Indenoisoquinolinone Analogs and Methods of Use Thereof

ABSTRACT

The present invention relates to Indenoisoquinolinone Analogs, compositions comprising an effective amount of an Indenoisoquinolinone Analog and methods for treating or preventing an inflammatory disease, a reperfusion injury, diabetes mellitus, a diabetic complication, reoxygenation injury resulting from organ transplantation, an ischemic condition, a neurodegenerative disease, renal failure, a vascular disease, a cardiovascular disease, cancer, a complication of prematurity, cardiomyopathy, retinopathy, nephropathy, neuropathy, erectile dysfunction or urinary incontinence, comprising administering to a subject in need thereof an effective amount of an Indenoisoquinolinone Analog.

1. REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.60/904,393, filed on Feb. 28, 2007, the disclosure of which isincorporated by reference herein in its entirety.

2. FIELD OF THE INVENTION

The present invention relates to Indenoisoquinolinone Analogs,compositions comprising an effective amount of an IndenoisoquinolinoneAnalog and methods for treating or preventing an inflammatory disease, areperfusion injury, diabetes mellitus, a diabetic complication,reoxygenation injury resulting from organ transplantation, an ischemiccondition, a neurodegenerative disease, renal failure, a vasculardisease, a cardiovascular disease, cancer, a complication ofprematurity, cardiomyopathy, retinopathy, nephropathy, neuropathy,erectile dysfunction or urinary incontinence, comprising administeringto a subject in need thereof an effective amount of anIndenoisoquinolinone Analog.

3. BACKGROUND OF THE INVENTION

Erectile dysfunction (“ED”) is a significant male-health issue. Whileestimating its prevalence is difficult, estimates range from about 15million to 30 million sufferers worldwide.

The etiology of erectile dysfunction can be multiple, and can includemechanical trauma to the nerves (such as during prostatectomy), or itcan be due to diabetes mellitus, cardiovascular diseases, induced byradiation, certain drugs, or advanced age.

Urinary incontinence affects people of all ages and levels of physicalhealth, both in health care settings and in the community at large.Persons suffering from urinary incontinence can be predisposed to alsohaving urinary-tract infections, pressure ulcers, perineal rashes andurosepsis. Psychosocially, urinary incontinence can be associated withembarrassment, social stigmatization, depression and a risk ofinstitutionalization (Herzo et al., Annu. Rev. Gerontol. Geriatr. 9:74(1989)).

An inflammatory disease, such as arthritis, colitis, and autoimmunediabetes, typically manifests itself as a disorder distinct from thatassociated with a reperfusion injury, e.g., stroke and heart attack, andcan clinically manifest itself as a different entity. However, there canbe common underlying mechanisms between these two types of disorders.Specifically, inflammatory disease and reperfusion injury can induceproinflammatory cytokine and chemokine synthesis which can, in turn,result in production of cytotoxic free radicals such as nitric oxide andsuperoxide. NO and superoxide can react to form peroxynitrite (ONOO⁻)(Szabó et al., Shock 6:79-88, 1996).

The ONOO⁻-induced cell necrosis observed in inflammatory disease and inreperfusion injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Activation of PARP is thought to be animportant step in the cell-mediated death observed in inflammation andreperfusion injury (Szabó al, Trends Pharmacol. Sci. 19:287-98, 1998).

A number of PARP inhibitors have been described in the art. See, e.g.,Banasik et al., J. Biol. Chem., 267:1569-75, 1992, and Banasik et al.,Mol. Cell. Biochem., 138:185-97, 1994; WO 00/39104; WO 00/39070; WO99/59975; WO 99/59973; WO 99/11649; WO 99/11645; WO 99/11644; WO99/11628; WO 99/11623; WO 99/11311; WO 00/42040; Zhang et al., Biochem.Biophys. Res. Commun., 278:590-98, 2000; White et al, J. Med. Chem.,43:4084-4097, 2000; Griffin et al., J. Med. Chem., 41:5247-5256, 1998;Shinkwin et al., Bioorg. Med. Chem., 7:297-308, 1999; and Soriano etal., Nature Medicine, 7:108-113, 2001. Adverse effects associated withadministration of PARP inhibitors have been discussed in Milan et al.,Science, 223:589-591, 1984.

Indenoisoquinolinone compounds have been previously discussed in theart. For example, cytotoxic non-camptothecin topoisomerase I inhibitorsare reported in Cushman et al., J. Med. Chem., 43:3688-3698, 2300 andCushman et al., J. Med. Chem. 42:446-57, 1999;indeno[1,2-c]isoquinolines are reported as antineoplastic agents inCushman et al., WO 00/21537; and as neoplasm inhibitors in Hrbata etal., WO 93/05023.

Syntheses of indenoisoquinolinone compounds have been reported. Forexample, see Wawzonek et al., Org. Prep. Proc. Int., 14:163-8, 1982;Wawzonek et al., Can. J. Chem., 59:2833, 1981; Andoi et al, Bull. Chem.Soc. Japan, 47:1014-17, 1974; Dusemund et al., Arch. Pharm (Weinheim,Ger.), 3 17:381-2, 1984; and Lal et al., Indian J. Chem., Sect. B,38B:33-39, 1999.

There remains, however, a need in the art for compounds useful fortreating or preventing an inflammatory disease, a reperfusion injury,diabetes mellitus, a diabetic complication, reoxygenation injuryresulting from organ transplantation, an ischemic condition, aneurodegenerative disease, renal failure, a vascular disease, acardiovascular disease, cancer, a complication of prematurity,cardiomyopathy, retinopathy, nephropathy, neuropathy, erectiledysfunction or urinary incontinence.

Citation of any reference in Section 3 of this application is not anadmission that the reference is prior art.

4. SUMMARY OF THE INVENTION

In one aspect the invention provides a compound of Formula (Ia)

and pharmaceutically acceptable salts thereof,wherein

X is —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or—N((CH₂)_(q)-Z)-;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

m is an integer ranging from 2 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In one aspect the invention provides a compound of Formula (Ib)

and pharmaceutically acceptable salts thereof,wherein

X is —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or—N((CH₂)_(q)-Z)-;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

m is an integer ranging from 2 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In one aspect the invention provides a compound of Formula (Ic)

and pharmaceutically acceptable salts thereof,wherein

X is —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or—N((CH₂)_(q)-Z)-;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, (C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

m is an integer ranging from 2 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In another aspect the invention provides a compound of Formula (IIa)

and pharmaceutically acceptable salts thereof;wherein

X is —CH₂—, —O—, —C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—;

R¹ is —(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl;

R³ is —C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle),a nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups;

or N, R² and R³ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle, which is substituted with one or moreof —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle) or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle) groups; and

an n is an integer ranging from 1 to 10.

In another aspect the invention provides a compound of Formula (IIb)

and pharmaceutically acceptable salts thereof,wherein

X is —CH₂—, —O—, —C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—;

R¹ is —(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl;

R³ is —C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle),a nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups;

or N, R² and R³ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle, which is substituted with one or moreof —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)—(nitrogen-containing 3- to 7-membered monocyclic heterocycle) or —(C₁-C₅alkylene)-(3- to 7-membered monocyclic heterocycle) groups; and

an n is an integer ranging from 1 to 10.

In another aspect the invention provides a compound of Formula (IIc)

and pharmaceutically acceptable salts thereof,wherein

X is —CH₂—, —O—, —C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—;

R¹ is —(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl;

R³ is —C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle),a nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups;

or N, R² and R³ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle, which is substituted with one or moreof —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)—(nitrogen-containing 3- to 7-membered monocyclic heterocycle) or —(C₁-C₅alkylene)-(3- to 7-membered monocyclic heterocycle) groups; and

an n is an integer ranging from 1 to 10.

In one aspect, the invention provides the following IndenoisoquinolinoneAnalogs according to Formula (IIIa) as set forth below:

(IIIa)

Compound —R¹ IIIa-1 

IIIa-2 

IIIa-3 

IIIa-4 

IIIa-5 

IIIa-6 

IIIa-7 

IIIa-8 

IIIa-9 

IIIa-10

IIIa-11

IIIa-12

IIIa-13

IIIa-14

IIIa-15

IIIa-16

IIIa-17

IIIa-18

IIIa-19

IIIa-20

IIIa-21

IIIa-22

IIIa-23

IIIa-24

and pharmaceutically acceptable salts thereof.

In another aspect, the invention provides the followingIndenoisoquinolinone Analogs according to Formula (IIIb) as set forthbelow:

(IIIb)

Compound —R¹ IIIb-1 

IIIb-2 

IIIb-3 

IIIb-4 

IIIb-5 

IIIb-6 

IIIb-7 

IIIb-8 

IIIb-9 

IIIb-10

IIIb-11

IIIb-12

IIIb-13

IIIb-14

IIIb-15

IIIb-16

IIIb-17

IIIb-18

IIIb-19

IIIb-20

IIIb-21

IIIb-22

IIIb-23

IIIb-24

and pharmaceutically acceptable salts thereof.

In one aspect the invention provides a compound of Formula (IVa)

and pharmaceutically acceptable salts thereof,wherein

X is —O—, —CH₂—, —C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—,—N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-;

R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In one aspect the invention provides a compound of Formula (IVb)

and pharmaceutically acceptable salts thereof,wherein

X is —O—, —CH₂—, —C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—,—N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-;

R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In one aspect the invention provides a compound of Formula (IVc)

and pharmaceutically acceptable salts thereof,wherein

X is —O—, —CH₂—, —C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—,—N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-;

R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle or a nitrogen-containing 7- to10-membered bicyclic heterocycle, each of which is unsubstituted orsubstituted with one or more of —C₁-C₅ alkyl, —C₃-C₈ monocycliccycloalkyl, phenyl, a nitrogen-containing 3- to 7-membered monocyclicheterocycle, -(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted)C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted)phenyl, -phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH,—O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle;

Z is —CF₃, —F, —OH or —O—CH₃;

n is an integer ranging from 1 to 10;

p is an integer ranging from 1 to 5; and

q is an integer ranging from 1 to 5.

In one aspect, the invention provides a compound of Formula (Va)

and pharmaceutically acceptable salts thereof,wherein

R¹ is —CH₂NH—R²;

R² is a —C₃-C₈ monocyclic cycloalkyl which is unsubstituted orsubstituted with one or more of -(hydroxy-substituted) C₁-C₅ alkyl; or a3- to 7-membered monocyclic heterocycle;

X is halo or —H; and

Y′ is halo or —H, wherein at least one of X and Y′ is halo.

The invention provides compositions comprising an effective amount of acompound of Formula (Ia), (Ib), (Ic), (IIa), (IIb), (IIc), (IIIa),(IIIb), (IVa), (IVb), (IVc), (Va), or a pharmaceutically acceptable saltthereof and a physiologically acceptable carrier or vehicle.

The invention further provides methods for treating or preventing aninflammatory disease, a reperfusion injury, diabetes mellitus, adiabetic complication, reoxygenation injury resulting from organtransplantation, an ischemic condition, a neurodegenerative disease,renal failure, a vascular disease, a cardiovascular disease, cancer, acomplication of prematurity, cardiomyopathy, retinopathy, nephropathy,neuropathy, erectile dysfunction or urinary incontinence (each being a“Condition”), comprising administering to a subject in need thereof aneffective amount of an Indenoisoquinolinone Analog of Formula (Ia),(Ib), (Ic), (IIa), (IIb), (IIc), (IIIa), (IIIb), (IVa), (IVb), (IVc),(Va), or a pharmaceutically acceptable salt thereof.

A compound of Formula (Ia), Formula (Ib), Formula (Ic), Formula (Ia),Formula (IIb), Formula (IIc), Formula (IIIa), Formula (IIIb), Formula(IVa), Formula (IVb), Formula (IVc), Formula (Va), or a pharmaceuticallyacceptable salt thereof (an “Indenoisoquinolinone Analog”) is useful fortreating or preventing a Condition.

A composition comprising an effective amount of an IndenoisoquinolinoneAnalog and a physiologically acceptable carrier or vehicle is useful fortreating or preventing a Condition.

The details of the invention are set forth in the accompanyingdescription below.

All patents and publications cited in this specification areincorporated by reference in their entirety.

5. DETAILED DESCRIPTION OF THE INVENTION 5.1 Definitions andAbbreviations

The following definitions are used in connection with theIndenoisoquinolinone Analogs:

The term “—C₁-C₃ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 3 carbon atoms, whereinone of the hydrocarbon's hydrogen atoms has been replaced by a singlebond. Representative straight chain —C₁-C₃ alkyls include -methyl,-ethyl, and -n-propyl. Representative branched —C₁-C₃ alkyls include-isopropyl.

The term “—C₁-C₄ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 4 carbon atoms, whereinone of the hydrocarbon's hydrogen atoms has been replaced by a singlebond. Representative straight chain —C₁-C₄ alkyls include -methyl,-ethyl, -n-propyl, and -n-butyl. Representative branched —C₁-C₄ alkylsinclude -isopropyl, -sec-butyl, -isobutyl and -tert-butyl. In oneembodiment, the —C₁-C₄ alkyl is substituted with one or more of -halo,—OH, —N(R³)₂, —(C₁-C₅ alkylene)-O—C₁-C₅ alkyl, —NH₂, anitrogen-containing 3- to 7-membered monocyclic heterocycle, or an—(C₁-C₆ alkyl-substituted) nitrogen-containing 3- to 7-memberedmonocyclic heterocycle. Unless otherwise indicated, the —C₁-C₄ alkyl isunsubstituted.

A “C₁-C₄ alkylene” refers to a C₁-C₄ alkyl group, as defined above,wherein one of the C₁-C₄ alkyl group's hydrogen atoms has been replacedwith a bond.

A “C₂-C₄ alkylene” refers to a straight or branched chain saturatedhydrocarbon containing 2-4 carbon atoms, wherein two of thehydrocarbon's hydrogen atoms have been replaced by a single a bond.Representative C₂-C₄ alkylene groups include, ethylene, n-propylene,isopropylene, n-butylene and isobutylene.

The term “—C₁-C₅ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 5 carbon atoms, whereinone of the hydrocarbon's hydrogen atoms has been replaced by a singlebond. Representative straight chain —C₁-C₅ alkyls include -methyl,-ethyl, -n-propyl, -n-butyl and -n-pentyl. Representative branched—C₁-C₅ alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl,-isopentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl,1,1-dimethylpropyl and 1,2-dimethylpropyl. In one embodiment, the —C₁-C₅alkyl is substituted with one or more of -halo, —OH, —N(R³)₂, —C₁-C₅alkylene-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or an —C₁-C₆ alkyl-substitutednitrogen-containing 3- to 7-membered monocyclic heterocycle. Unlessotherwise indicated, the —C₁-C₅ alkyl is unsubstituted.

A “C₁-C₅ alkylene” refers to a C₁-C₅ alkyl group, as defined above,wherein one of the C₁-C₅ alkyl group's hydrogen atoms has been replacedwith a bond.

The term “-phenyl-substituted C₁-C₅ alkyl” as used herein, refers to a“—C₁-C₅ alkyl” wherein one of the its hydrogen atoms has been replacedby a phenyl group.

The term “—C₁-C₆ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 6 carbon atoms, whereinone of the hydrocarbon's hydrogen atoms has been replaced by a singlebond. Representative straight chain —C₁-C₆ alkyls include -methyl,-ethyl, -n-propyl, -n-butyl, -n-pentyl and -n-hexyl. Representativebranched —C₁-C₆ alkyls include -isopropyl, -sec-butyl, -isobutyl,-tert-butyl, -isopentyl, -neopentyl, -1-methylbutyl, -isohexyl,-neohexyl, -2-methylbutyl, -3-methylbutyl, -1,1-dimethylpropyl and-1,2-dimethylpropyl. In one embodiment, the —C₁-C₆ alkyl is substitutedwith one or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl,—O—C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, a 3- to 7-memberedmonocyclic heterocycle, —(C₁-C₆ alkyl-substituted) 3- to 7-memberedmonocyclic heterocycle, or —N(Z₃)(Z₄). Unless otherwise indicated, the—C₁-C₆ alkyl is unsubstituted.

A “C₁-C₆ alkylene” refers to a C₁-C₆ alkyl group, as defined above,wherein one of the C₁-C₆ alkyl group's hydrogen atoms has been replacedwith a bond.

The term “—C₂-C₆ alkenyl” refers to a straight or branched chainhydrocarbon containing 2-6 carbon atoms and at least one double bond.Representative C₂-C₆ alkenyl groups include, but are not limited to,ethylene, propylene, 1-butylene, 2-butylene, isobutylene, sec-butylene,1-pentene, 2-pentene, isopentene, 1-hexene, 2-hexene, 3-hexene andisohexene.

The term “—C₁-C₈ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 9 carbon atoms, whereinone of the hydrocarbon's hydrogen atoms has been replaced by a singlebond. Representative —C₁-C₉ alkyls include, methyl, ethyl, propyl,butyl, pentyl, hexyl, heptyl, octyl, -nonyl, isopropyl, isobutyl,sec-butyl and tert-butyl, isopentyl, neopentyl, isohexyl, isoheptyl,isooctyl and isononyl.

The term “—C₇-C₁₀ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 7 to 10 carbon atoms,wherein one of the hydrocarbon's hydrogen atoms has been replaced by asingle bond. Representative —C₇-C₁₀ alkyls include, but are not limitedto, heptyl, octyl, nonyl, isohexyl, isoheptyl, isooctyl and isononyl,decyl, and isodecyl.

The term “—C₁-C₁₀ alkyl” as used herein, refers to a straight chain orbranched non-cyclic hydrocarbon having from 1 to 10 carbon atoms,wherein one of the hydrocarbon's hydrogen atoms has been replaced by asingle bond. Representative —C₁-C₁₀ alkyls include, methyl, ethyl,propyl, butyl, pentyl, hexyl, heptyl, octyl, -nonyl, decyl, isopropyl,isobutyl, sec-butyl and tert-butyl, isopentyl, neopentyl, isohexyl,isoheptyl, isooctyl, isononyl and isodecyl.

The term “—C₃-C₈ monocyclic cycloalkyl” as used herein, refers to asaturated cyclic hydrocarbon having from 3 to 8 carbon atoms.Representative —C₃-C₈ monocyclic cycloalkyls include -cyclopropyl,-cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl and -cyclooctyl. Inone embodiment, the —C₃-C₈ monocyclic cycloalkyl is substituted with oneor more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆alkyl, —C₃-C₈ monocyclic cycloalkyl, a 3- to 7-membered monocyclicheterocycle, —C₁-C₆ alkyl-substituted 3- to 7-membered monocyclicheterocycle. In another embodiment, the —C₃-C₈ monocyclic cycloalkyl issubstituted with one or more of —N(R³)₂, —C₁-C₅ alkylene-O—C₁-C₅ alkyl,or —NH₂. Unless otherwise indicated, the —C₃-C₈ monocyclic cycloalkyl isunsubstituted.

A “nitrogen containing 3- to 7-membered monocyclic heterocycle” refersto a monocyclic 3- to 7-membered aromatic or non-aromatic monocycliccycloalkyl group in which one of the cycloalkyl group's ring carbonatoms has been replaced with a nitrogen atom and 0-4 of the cycloalkylgroup's remaining ring carbon atoms are independently replaced with a N,O or S atom. The nitrogen containing 3- to 7-membered monocyclicheterocycles can be attached via a nitrogen, sulfur, or carbon atom.Representative examples of nitrogen-containing-3- to 7-memberedmonocyclic heterocycles include, but are not limited to, piperidinyl,piperazinyl, pyrrolyl, piperidonyl, oxazinyl, thiazinyl, diazinyl,triazinyl, tetrazinyl, imidazolyl, tetrazolyl, pyrrolidinyl, isoxazolyl,pyridinyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, pyrimidinyl,morpholinyl, furuzanyl, pyrrolinyl, imidazolinyl, imidazolidinyl,pyrazolinyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridazinyl,pyrazinyl, pyrazolidinyl, and thiomorpholinyl.

In one embodiment, the nitrogen-containing 3- to 7-membered monocyclicheterocycle is fully saturated or partially saturated.

In another embodiment, the nitrogen-containing 3- to 7-memberedmonocyclic heterocycle is substituted with one or more of -halo, —OH,—OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocycliccycloalkyl, a 3- to 7-membered monocyclic heterocycle, —(C₁-C₆alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄). Unless otherwise indicated, the nitrogen-containing 3- to7-membered monocyclic heterocycle is unsubstituted.

A “nitrogen-containing 7- to 10-membered bicyclic heterocycle” refers toa 7- to 10-membered bicyclic ring system that contains at least one ringnitrogen atom. The nitrogen-containing 7- to 10-membered bicyclicheterocycles can be attached via a nitrogen, sulfur, or carbon atom.Representative nitrogen-containing 7- to 10-membered bicyclicheterocycles include -quinolinyl, -isoquinolinyl, -chromonyl, -indolyl,-isoindolyl, -indolinyl, indolizinyl, -indazolyl, -purinyl,-4H-quinolizinyl, -isoquinolyl, -quinolyl, -phthalazinyl,-naphthyridinyl, benzimidazolyl, benzthiazolyl, dihydroquinolyl,dihydroisoquinolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, andpteridyl.

In one embodiment, the nitrogen-containing 7- to 10-membered bicyclicheterocycle is saturated or partially saturated.

A “3- to 7-membered monocyclic heterocycle” refers to a monocyclic 3- to7-membered aromatic or non-aromatic monocyclic cycloalkyl in which 1-4of the ring carbon atoms have been independently replaced with a N, O orS atom. The 3- to 7-membered monocyclic heterocycles can be attached viaa nitrogen, sulfur, or carbon atom. Representative examples of a 3- to7-membered monocyclic heterocycle group include, but are not limited to,nitrogen-containing 3- to 7-membered monocyclic heterocycles discussedabove, tetrahydrofuranyl, dihydrofuranyl, pyranyl, dihydropyranyl,tetrahydropyranyl, thiopyranyl, dihydrothiopyranyl,tetrahydrothiopyranyl, dioxanyl, dithianyl, trithianyl, dioxolanyl,furanyl, and thiophenyl. In one embodiment, the 3- to 7-memberedmonocyclic heterocycle is a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle. In another embodiment, the 3- to 7-memberedmonocyclic heterocycle is saturated or partially saturated.

A “C₁-C₆ alkyl-substituted 3- to 7-membered monocyclic heterocycle”refers to a “3- to 7-membered monocyclic heterocycle,” as defined above,wherein one or more of the heterocycle's hydrogen atoms has beenreplaced by a C₁-C₆ alkyl, as defined above.

“Halo” is —F, —Cl, —Br or —I.

“Halo-substituted C₁-C₅ alkyl” refers to a C₁-C₅ alkyl group, as definedabove, wherein one or more of the C₁-C₅ alkyl group's hydrogen atoms hasbeen replaced with —F, —Cl, —Br or —I. Representative examples of ahalo-substituted C₁-C₅ alkyl include, but are not limited to, —CH₂F,—CCl₃, —CF₃, —CH₂Cl, —CH₂CH₂Br, —CH₂CH₂I, —CH₂CH₂CH₂F, —CH₂CH₂CH₂Cl,—CH₂CH₂CH₂CH₂Br, —CH₂CH₂CH₂CH₂I, —CH₂CH₂CH₂CH₂CH₂Br, —CH₂CH₂CH₂CH₂CH₂T,—CH₂CH(Br)CH₃, —CH₂CH(Cl)CH₂CH₃, —CH(F)CH₂CH₃ and —C(CH₃)₂(CH₂Cl).

“Halo-substituted phenyl” refers to a phenyl group, wherein one or moreof the phenyl group's hydrogen atoms has been replaced with —F, Cl, —Bror —I.

“Cyano-substituted phenyl” refers to a phenyl group, wherein one or moreof the phenyl group's hydrogen atoms has been replaced with —CN.

“Cyano-substituted C₁-C₅ alkyl” refers to a C₁-C₅ alkyl group, asdefined above, wherein one or more of the C₁-C₅ alkyl group's hydrogenatoms has been replaced with —CN. Representative examples of acyano-substituted C₁-C₅ alkyl include, but are not limited to, —CH₂CN,—CH₂CH₂CN, —CH₂CH₂CH₂CN, —CH₂CH₂CH₂CH₂CN, —CH₂CH₂CH₂CH₂CH₂CN,—CH₂CH(CN)CH₃, —CH₂CH(CN)CH₂CH₃, —CH(CN)CH₂CH₃ and —C(CH₃)₂(CH₂CN).

A “C₁-C₆ alkylene phenyl” refers to a C₁-C₆ alkyl group, as definedabove, wherein one of the C₁-C₆ alkyl group's hydrogen atoms has beenreplaced with phenyl.

“Hydroxy-substituted C₁-C₅ alkyl” refers to a C₁-C₅ alkyl group, asdefined above, wherein one or more of the C₁-C₅ alkyl group's hydrogenatoms has been replaced with —OH. Representative examples of ahydroxy-substituted C₁-C₅ alkyl include, but are not limited to, —CH₂OH,—CH₂CH₂OH, —CH₂CH₂CH₂OH, —CH₂CH₂CH₂CH₂OH, —CH₂CH₂CH₂CH₂CH₂OH,—CH₂CH(OH)CH₃, —CH₂CH(OH)CH₂CH₃, —CH(OH)CH₂CH₃ and —C(CH₃)₂(CH₂OH).

A “C-terminal alpha amino acid residue” refers to an L-, D- or racemicnatural or unnatural alpha amino acid, less the hydroxyl group of thealpha amino acid's carboxyl group. Representative examples of aC-terminal alpha amino acid residue include, but are not limited to,CH₃—CH(NH₂)—C(O)—, HN═C(NH₂)—NH—(CH₂)₃—CH(NH₂)—C(O)—,H₂N—C(O)—CH₂—CH(NH₂)—C(O)—, HOOC—CH₂—CH(NH₂)—C(O)—,HS—CH₂—CH(NH₂)—C(O)—, H₂N—C(O)—(CH₂)₂—CH(NH₂)—C(O)—,HOOC—(CH₂)₂—CH(NH₂)—C(O)—, H₂N—CH₂—C(O)—, CH₃—CH₂—CH(CH₃)—CH(NH₂)—C(O)—,(CH₃)₂—CH—CH₂—CH(NH₂)—C(O)—, H₂N—(CH₂)₄—CH(NH₂)—C(O)—,CH₃—S—(CH₂)₂—CH(NH₂)—C(O)—, HO—CH₂—CH(NH₂)—C(O)—,CH₃—CH(OH)—CH(NH₂)—C(O)—,

(CH₃)₂—CH—CH(NH₂)—C(O)—,

In one embodiment, the C-terminal alpha amino acid is a natural aminoacid.

In another embodiment, the C-terminal alpha amino acid is an unnaturalamino acid.

In one embodiment, the C-terminal alpha amino acid is an L amino acid.

An “N-terminal alpha amino acid residue” refers to an L-, D- or racemicnatural or unnatural alpha amino acid, less the alpha amino acid'sN-terminal amino group. Representative examples of an N-terminal alphaamino acid residue include, but are not limited to, —CH₂—COOH,—CH(CH₃)COOH, —CH(CH(CH₃)₂)COOH, —CH(CH₂CH(CH₃)₂)COOH,—CH(CH(CH₃)(CH₂CH₃))COOH, —CH((CH₂)₄—NH₂)COOH,—CH((CH₂)₃NH(C═NH₂)—NH₂)COOH, —CH(CH₂—OH)COOH, —CH(CH((CH₃)(OH)))COOH,—CH(CH₂—COOH)COOH, —CH((CH₂)₂COOH)COOH, —CH((CH₂)(CONH₂))COOH,—CH((CH₂)₂(CONH₂))COOH, —CH(CH₂—SH)COOH, —CH((CH₂)₂—S—CH₃)COOH,

In one embodiment, the N-terminal alpha amino acid residue issubstituted with one or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH,—C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, a 3- to7-membered monocyclic heterocycle, —C₁-C₆ alkyl-substituted 3- to7-membered monocyclic heterocycle, or —N(Z₃)(Z₄). Unless otherwiseindicated, the N-terminal alpha amino acid residue is unsubstituted.

An “N-terminal alpha amino hydroxymethyl residue” refers to an“N-terminal alpha amino acid residue,” wherein its C-terminal carboxylgroup, a side chain's carboxyl group, or both have been replaced with ahydroxymethyl group. In one embodiment, the N-terminal alpha aminohydroxymethyl residue is substituted with one or more of -halo, —OH,—OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocycliccycloalkyl, a 3- to 7-membered monocyclic heterocycle, —C₁-C₆alkyl-substituted 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄). In another embodiment, the hydroxyl group of thehydroxymethyl residue is substituted with —PO₃H₂, —P₂O₆H₃, —P₃O₉H₄,—SO₃H, —C(O)—C₁-C₉ alkyl, β-D-glucuronyl, or a C-terminal alpha aminoacid residue. Unless otherwise indicated, the N-terminal alpha aminohydroxymethyl residue is unsubstituted.

A “C₁-C₆ alkyl ester of an N-terminal alpha amino acid residue” refersto an “N-terminal alpha amino acid residue,” wherein the hydrogen atomof the amino acid's C-terminal carboxyl group, a side chain's carboxylgroup, or both have been replaced by a —C₁-C₆ alkyl group. In oneembodiment, the C₁-C₆ alkyl ester of an N-terminal alpha amino acidresidue is a methyl, an ethyl, an n-propyl or an iso-propyl ester of anN-terminal alpha amino acid residue. In another embodiment, the C₁-C₆alkyl ester of an N-terminal alpha amino acid residue is substitutedwith one or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl,—O—C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, a 3- to 7-memberedmonocyclic heterocycle, —C₁-C₆ alkyl-substituted 3- to 7-memberedmonocyclic heterocycle, or —N(Z₃)(Z₄). Unless otherwise indicated, theC₁-C₆ alkyl ester of an N-terminal alpha amino acid residue isunsubstituted.

In one embodiment, the N-terminal alpha amino acid is a natural aminoacid.

In another embodiment, the N-terminal alpha amino acid is an unnaturalamino acid.

In one embodiment, the N-terminal alpha amino acid is an L amino acid.

A “β-D-glucuronyl” refers to a group having the formula:

A “subject” is a mammal, e.g., a human, mouse, rat, guinea pig, dog,cat, horse, cow, pig, or non-human primate, such as a monkey,chimpanzee, baboon or rhesus. In one embodiment, the subject is a human.

The phrase “pharmaceutically acceptable salt,” as used herein, is a saltof an acid and a basic nitrogen atom of an Indenoisoquinolinone Analog.Illustrative salts include, but are not limited, to sulfate, citrate,acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate,phosphate, acid phosphate, isonicotinate, lactate, salicylate, acidcitrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate,succinate, maleate, gentisinate, fumarate, gluconate, glucaronate,saccharate, formate, benzoate, glutamate, methanesulfonate,ethanesulfonate, benzenesulfonate, p-toluenesulfonate, camphorsulfonate,and pamoate (i.e., 1,1′-methylene-bis-(2-hydroxy-3-naphthoate)) salts.The term “pharmaceutically acceptable salt” also refers to a salt of anIndenoisoquinolinone Analog having an acidic functional group, such as acarboxylic acid functional group, and a base. Suitable bases include,but are not limited to, hydroxides of alkali metals such as sodium,potassium, and lithium; hydroxides of alkaline earth metal such ascalcium and magnesium; hydroxides of other metals, such as aluminum andzinc; ammonia, and organic amines, such as unsubstituted orhydroxy-substituted mono-, di-, or tri-alkylamines, dicyclohexylamine;tributyl amine; pyridine; N-methyl, N-ethylamine; diethylamine;triethylamine; mono-, bis-, or tris-(2-OH-lower alkylamines), such asmono-; bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine,or tris-(hydroxymethyl)methylamine, N,N-di-lower alkyl-N-(hydroxyl-loweralkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine ortri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such asarginine, lysine, and the like. The term “pharmaceutically acceptablesalt” also includes a hydrate of a compound of the invention.

In one embodiment, the pharmaceutically acceptable salt is a mesylatesalt.

In another embodiment, the pharmaceutically acceptable salt is acamphorsulfonate salt.

An “effective amount” when used in connection with anIndenoisoquinolinone Analog is an amount that is effective for treatingor preventing a Condition.

An “effective amount” when used in connection with another anticanceragent is an amount that is effective for treating or preventing canceralone or in combination with an Indenoisoquinolinone Analog. “Incombination with” includes administration within the same compositionand via separate compositions. In the latter instance, the otheranticancer agent is administered during a time when theIndenoisoquinolinone Analog exerts its prophylactic or therapeuticeffect, or vice versa.

The following abbreviations are used herein and have the indicateddefinitions: DMF is N,N-dimethylformamide, THF is tetrahydrofuran, DMACis dimethylacetamide. DMSO is dimethylsulfoxide, Et is ethyl, Pr isn-propyl, i-Pr is isopropyl, EtOAc is ethyl acetate, EtOH is ethanol, Meis methyl, MS is mass spectrometry, Ts is tosylate, Tf is triflate, Phis phenyl, NMR is Nuclear Magnetic Resonance, Ms is mesylate, LAH islithium aluminum hydride and tBoc is t-butyloxycarbonyl.

5.2 The Indenoisoquinolinone Analogs of Formula (Ia)

The present invention provides Indenoisoquinolinone Analogs according toFormula (Ia), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (Ia).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂ CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(C(CH₃)₃)—.

In one embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In one embodiment, X is —CH(OH)—.

In another embodiment, X is —CH(OH)— and R¹ is —(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —CH(OH)— and R¹ is —(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R¹)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, m is 2.

In another embodiment, m is 3.

In yet another embodiment, m is 4, 5, or 6.

In a further embodiment, m is 7, 8, or 9.

In yet a further embodiment, m is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl;

n is an integer ranging from 1 to 10; and

m is an integer ranging from 2 to 10.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at least one R² is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at least one R² is —C₃-C₈monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein N and both R² groupsare taken together to form a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, which is substituted with a hydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle, which is substituted with anitrogen-containing 3- to 7-membered monocyclic heterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (Ia) as set forth below:

(Ia)

Compound n —R¹ X Ia-1   1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ia-2   2—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ia-3   3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ia-4  4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ia-5   5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)—Ia-6   6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ia-7   1 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₃)— Ia-8   2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ia-9   3—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ia-10  4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)—Ia-11  5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ia-12  6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₃)— Ia-13  1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-14  2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-15  3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ia-16  4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-17  5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-18  6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ia-19  1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-20  2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-21  3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ia-22  4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-23  5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-24  6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ia-25  1 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ia-26  2 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-27  3—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-28  4 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-29  5 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-30  6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-31  1 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)—Ia-32  2 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-33  3 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ia-34  4 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-35  5—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-36  6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ia-37  1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)_(2)—) Ia-38 2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)_(2)—) Ia-39  3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂C(H)(CH₃)_(2)—) Ia-40  4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)_(2)—)Ia-41  5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)_(2)—) Ia-42  6—(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)_(2)—) Ia-43  1 —(CH₂)_(n)—N(CH₃)₂—N(C(CH₃)₃)— Ia-44  2 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ia-45  3—(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ia-46  4 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)—Ia-47  5 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ia-48  6 —(CH₂)_(n)—N(CH₃)₂—N(C(CH₃)₃)— Ia-49  1

—N(CH₃)— Ia-50  2

—N(CH₃)— Ia-51  3

—N(CH₃)— Ia-52  4

—N(CH₃)— Ia-53  5

—N(CH₃)— Ia-54  6

—N(CH₃)— Ia-55  1

—N(CH₂CH₃)— Ia-56  2

—N(CH₂CH₃)— Ia-57  3

—N(CH₂CH₃)— Ia-58  4

—N(CH₂CH₃)— Ia-59  5

—N(CH₂CH₃)— Ia-60  6

—N(CH₂CH₃)— Ia-61  1

—N(CH₂CH₂CH₃)— Ia-62  2

—N(CH₂CH₂CH₃)— Ia-63  3

—N(CH₂CH₂CH₃)— Ia-64  4

—N(CH₂CH₂CH₃)— Ia-65  5

—N(CH₂CH₂CH₃)— Ia-66  6

—N(CH₂CH₂CH₃)— Ia-67  1

—N(CH₂CH₂CH₂CH₃)— Ia-68  2

—N(CH₂CH₂CH₂CH₃)— Ia-69  3

—N(CH₂CH₂CH₂CH₃)— Ia-70  4

—N(CH₂CH₂CH₂CH₃)— Ia-71  5

—N(CH₂CH₂CH₂CH₃)— Ia-72  6

—N(CH₂CH₂CH₂CH₃)— Ia-73  1

—N(C(H)(CH₃)(CH₂CH₃))— Ia-74  2

—N(C(H)(CH₃)(CH₂CH₃))— Ia-75  3

—N(C(H)(CH₃)(CH₂CH₃))— Ia-76  4

—N(C(H)(CH₃)(CH₂CH₃))— Ia-77  5

—N(C(H)(CH₃)(CH₂CH₃))— Ia-78  6

—N(C(H)(CH₃)(CH₂CH₃))— Ia-79  1

—N(C(H)(CH₃)₂)— Ia-80  2

—N(C(H)(CH₃)₂)— Ia-81  3

—N(C(H)(CH₃)₂)— Ia-82  4

—N(C(H)(CH₃)₂)— Ia-83  5

—N(C(H)(CH₃)₂)— Ia-84  6

—N(C(H)(CH₃)₂)— Ia-85  1

—N(CH₂C(H)(CH₃)₂)— Ia-86  2

—N(CH₂C(H)(CH₃)₂)— Ia-87  3

—N(CH₂C(H)(CH₃)₂)— Ia-88  4

—N(CH₂C(H)(CH₃)₂)— Ia-89  5

—N(CH₂C(H)(CH₃)₂)— Ia-90  6

—N(CH₂C(H)(CH₃)₂)— Ia-91  1

—N(C(CH₃)₃)— Ia-92  2

—N(C(CH₃)₃)— Ia-93  3

—N(C(CH₃)₃)— Ia-94  4

—N(C(CH₃)₃)— Ia-95  5

—N(C(CH₃)₃)— Ia-96  6

—N(C(CH₃)₃)— Compound m —R¹ X Ia-146  2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ia-147  3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ia-148  4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₃)— Ia-149  5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ia-150  6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ia-151  2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ia-152  3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ia-153  4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ia-154  5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ia-155  6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ia-156  2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ia-157  3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ia-158  4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-159  5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-160  6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ia-161  2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-162  3—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-163  4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ia-164  5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-165 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-166  2 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ia-167  3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)—Ia-168  4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-169  5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-170  6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-171  2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-172  3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-173  4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-174  5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-175  6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-176  2 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)—Ia-178  3 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-179  4—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-180  5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ia-181  6 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-182  2—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-183  3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ia-184  4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)—Ia-185  5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-186  6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-187  2

—N(CH₃)— Ia-188  3

—N(CH₃)— Ia-189  4

—N(CH₃)— Ia-190  5

—N(CH₃)— Ia-191  6

—N(CH₃)— Ia-192  2

—N(CH₃)— Ia-193  3

—N(CH₂CH₃)— Ia-194  4

—N(CH₂CH₃)— Ia-195  5

—N(CH₂CH₃)— Ia-196  6

—N(CH₂CH₃)— Ia-197  2

—N(CH₂CH₃)— Ia-198  3

—N(CH₂CH₃)— Ia-199  4

—N(CH₂CH₂CH₃)— Ia-200  5

—N(CH₂CH₂CH₃)— Ia-201  6

—N(CH₂CH₂CH₃)— Ia-202  2

—N(CH₂CH₂CH₃)— Ia-203  3

—N(CH₂CH₂CH₃)— Ia-204  4

—N(CH₂CH₂CH₃)— Ia-205  5

—N(CH₂CH₂CH₂CH₃)— Ia-206  6

—N(CH₂CH₂CH₂CH₃)— Ia-207  2

—N(CH₂CH₂CH₂CH₃)— Ia-208  3

—N(CH₂CH₂CH₂CH₃)— Ia-209  4

—N(CH₂CH₂CH₂CH₃)— Ia-210  5

—N(CH₂CH₂CH₂CH₃)— Ia-211  6

—N(C(H)(CH₃)(CH₂CH₃))— Ia-212  2

—N(C(H)(CH₃)(CH₂CH₃))— Ia-213  3

—N(C(H)(CH₃)(CH₂CH₃))— Ia-214  4

—N(C(H)(CH₃)(CH₂CH₃))— Ia-215  5

—N(C(H)(CH₃)(CH₂CH₃))— Ia-216  6

—N(C(H)(CH₃)(CH₂CH₃))— Ia-217  2

—N(C(H)(CH₃)₂)— Ia-218  3

—N(C(H)(CH₃)₂)— Ia-219  4

—N(C(H)(CH₃)₂)— Ia-220  5

—N(C(H)(CH₃)₂)— Ia-221  6

—N(C(H)(CH₃)₂)— Ia-222  2

—N(C(H)(CH₃)₂)— Ia-223  3

—N(CH₂C(H)(CH₃)₂)— Ia-224  4

—N(CH₂C(H)(CH₃)₂)— Ia-225  5

—N(CH₂C(H)(CH₃)₂)— Ia-226  6

—N(CH₂C(H)(CH₃)₂)— Compound —R¹ X Ia-267  —CH₂—N(CH₂—CH₃)₂ —N(CH₃)—Ia-268  —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₃)— Ia-269  —CH₂—N(CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ia-270  —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-271 —CH₂—N(CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-272  —CH₂—N(CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ia-273  —CH₂—N(CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-274 —CH₂—N(CH₂—CH₃)₂ —N(C(CH₃)₃)— Ia-275  —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₃)—Ia-276  —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₃)— Ia-277  —CH₂—N(CH₂—CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ia-278  —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-279 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-280  —CH₂—N(CH₂—CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ia-281  —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-282 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(CH₃)₃)— Ia-283  —CH₂—N(CH₂—CH₂OH)₂ —N(CH₃)—Ia-284  —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₃)— Ia-285  —CH₂—N(CH₂—CH₂OH)₂—N(CH₂CH₂CH₃)— Ia-286  —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₂CH₂CH₃)— Ia-287 —CH₂—N(CH₂—CH₂OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-288  —CH₂—N(CH₂—CH₂OH)₂—N(C(H)(CH₃)₂)— Ia-289  —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂C(H)(CH₃)₂)— Ia-290 —CH₂—N(CH₂—CH₂OH)₂ —N(C(CH₃)₃)— Ia-291  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(CH₃)— Ia-292  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₃)— Ia-293 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ia-294  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(CH₂CH₂CH₂CH₃)— Ia-295  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(C(H)(CH₃)(CH₂CH₃))— Ia-296  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)₂)—Ia-297  —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)— Ia-298 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(CH₃)₃)— Ia-299 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₃)— Ia-300 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₃)— Ia-301 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ia-302 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₂CH₃)— Ia-303 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-304 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)₂)— Ia-305 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)— Ia-306 —CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(CH₃)₃)— Ia-307 

—N(CH₃)— Ia-308 

—N(CH₂CH₃)— Ia-309 

—N(CH₂CH₂CH₃)— Ia-310 

—N(CH₂CH₂CH₂CH₃)— Ia-311 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-312 

—N(C(H)(CH₃)₂)— Ia-313 

—N(CH₂C(H)(CH₃)₂)— Ia-314 

—N(C(CH₃)₃)— Ia-315 

—N(CH₃)— Ia-316 

—N(CH₂CH₃)— Ia-317 

—N(CH₂CH₂CH₃)— Ia-318 

—N(CH₂CH₂CH₂CH₃)— Ia-319 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-320 

—N(C(H)(CH₃)₂)— Ia-321 

—N(CH₂C(H)(CH₃)₂)— Ia-322 

—N(C(CH₃)₃)— Ia-323 

—N(CH₃)— Ia-324 

—N(CH₂CH₃)— Ia-325 

—N(CH₂CH₂CH₃)— Ia-326 

—N(CH₂CH₂CH₂CH₃)— Ia-327 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-328 

—N(C(H)(CH₃)₂)— Ia-329 

—N(CH₂C(H)(CH₃)₂)— Ia-330 

—N(C(CH₃)₃)— Ia-331 

—N(CH₃)— Ia-332 

—N(CH₂CH₃)— Ia-333 

—N(CH₂CH₂CH₃)— Ia-334 

—N(CH₂CH₂CH₂CH₃)— Ia-335 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-336 

—N(C(H)(CH₃)₂)— Ia-337 

—N(CH₂C(H)(CH₃)₂)— Ia-338 

—N(C(CH₃)₃)— Ia-339 

—N(CH₃)— Ia-340 

—N(CH₂CH₃)— Ia-341 

—N(CH₂CH₂CH₃)— Ia-342 

—N(CH₂CH₂CH₂CH₃)— Ia-343 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-344 

—N(C(H)(CH₃)₂)— Ia-345 

—N(CH₂C(H)(CH₃)₂)— Ia-346 

—N(C(CH₃)₃)— Ia-347 

—N(CH₃)— Ia-348 

—N(CH₂CH₃)— Ia-349 

—N(CH₂CH₂CH₃)— Ia-350 

—N(CH₂CH₂CH₂CH₃)— Ia-351 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-352 

—N(C(H)(CH₃)₂)— Ia-353 

—N(CH₂C(H)(CH₃)₂)— Ia-354 

—N(C(CH₃)₃)— Ia-355 

—N(CH₃)— Ia-356 

—N(CH₂CH₃)— Ia-357 

—N(CH₂CH₂CH₃)— Ia-358 

—N(CH₂CH₂CH₂CH₃)— Ia-359 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-360 

—N(C(H)(CH₃)₂)— Ia-361 

—N(CH₂C(H)(CH₃)₂)— Ia-362 

—N(C(CH₃)₃)— Ia-363 

—N(CH₃)— Ia-364 

—N(CH₂CH₃)— Ia-365 

—N(CH₂CH₂CH₃)— Ia-366 

—N(CH₂CH₂CH₂CH₃)— Ia-367 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-368 

—N(C(H)(CH₃)₂)— Ia-369 

—N(CH₂C(H)(CH₃)₂)— Ia-370 

—N(C(CH₃)₃)— Ia-371 

—N(CH₃)— Ia-372 

—N(CH₂CH₃)— Ia-373 

—N(CH₂CH₂CH₃)— Ia-374 

—N(CH₂CH₂CH₂CH₃)— Ia-375 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-376 

—N(C(H)(CH₃)₂)— Ia-377 

—N(CH₂C(H)(CH₃)₂)— Ia-378 

—N(C(CH₃)₃)— Ia-379 

—N(CH₃)— Ia-380 

—N(CH₂CH₃)— Ia-381 

—N(CH₂CH₂CH₃)— Ia-382 

—N(CH₂CH₂CH₂CH₃)— Ia-383 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-384 

—N(C(H)(CH₃)₂)— Ia-385 

—N(CH₂C(H)(CH₃)₂)— Ia-386 

—N(C(CH₃)₃)— Ia-387 

—N(CH₃)— Ia-388 

—N(CH₂CH₃)— Ia-389 

—N(CH₂CH₂CH₃)— Ia-390 

—N(CH₂CH₂CH₂CH₃)— Ia-391 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-392 

—N(C(H)(CH₃)₂)— Ia-393 

—N(CH₂C(H)(CH₃)₂)— Ia-394 

—N(C(CH₃)₃)— Ia-395 

—N(CH₃)— Ia-396 

—N(CH₂CH₃)— Ia-397 

—N(CH₂CH₂CH₃)— Ia-398 

—N(CH₂CH₂CH₂CH₃)— Ia-399 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-400 

—N(C(H)(CH₃)₂)— Ia-401 

—N(CH₂C(H)(CH₃)₂)— Ia-402 

—N(C(CH₃)₃)— Ia-403 

—N(CH₃)— Ia-404 

—N(CH₂CH₃)— Ia-405 

—N(CH₂CH₂CH₃)— Ia-406 

—N(CH₂CH₂CH₂CH₃)— Ia-407 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-408 

—N(C(H)(CH₃)₂)— Ia-409 

—N(CH₂C(H)(CH₃)₂)— Ia-410 

—N(C(CH₃)₃)— Ia-411 

—N(CH₃)— Ia-412 

—N(CH₂CH₃)— Ia-413 

—N(CH₂CH₂CH₃)— Ia-414 

—N(CH₂CH₂CH₂CH₃)— Ia-415 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-416 

—N(C(H)(CH₃)₂)— Ia-417 

—N(CH₂C(H)(CH₃)₂)— Ia-418 

—N(C(CH₃)₃)— Ia-419 

—N(CH₃)— Ia-420 

—N(CH₂CH₃)— Ia-421 

—N(CH₂CH₂CH₃)— Ia-422 

—N(CH₂CH₂CH₂CH₃)— Ia-423 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-424 

—N(C(H)(CH₃)₂)— Ia-425 

—N(CH₂C(H)(CH₃)₂)— Ia-426 

—N(C(CH₃)₃)— Ia-427 

—N(CH₃)— Ia-428 

—N(CH₂CH₃)— Ia-429 

—N(CH₂CH₂CH₃)— Ia-430 

—N(CH₂CH₂CH₂CH₃)— Ia-431 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-432 

—N(C(H)(CH₃)₂)— Ia-433 

—N(CH₂C(H)(CH₃)₂)— Ia-434 

—N(C(CH₃)₃)— Ia-435 

—N(CH₃)— Ia-436 

—N(CH₂CH₃)— Ia-437 

—N(CH₂CH₂CH₃)— Ia-438 

—N(CH₂CH₂CH₂CH₃)— Ia-439 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-440 

—N(C(H)(CH₃)₂)— Ia-441 

—N(CH₂C(H)(CH₃)₂)— Ia-442 

—N(C(CH₃)₃)— Ia-443 

—N(CH₃)— Ia-444 

—N(CH₂CH₃)— Ia-445 

—N(CH₂CH₂CH₃)— Ia-446 

—N(CH₂CH₂CH₂CH₃)— Ia-447 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-448 

—N(C(H)(CH₃)₂)— Ia-449 

—N(CH₂C(H)(CH₃)₂)— Ia-450 

—N(C(CH₃)₃)— Ia-451 

—N(CH₃)— Ia-452 

—N(CH₂CH₃)— Ia-453 

—N(CH₂CH₂CH₃)— Ia-454 

—N(CH₂CH₂CH₂CH₃)— Ia-455 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-456 

—N(C(H)(CH₃)₂)— Ia-457 

—N(CH₂C(H)(CH₃)₂)— Ia-458 

—N(C(CH₃)₃)— Ia-459 

—N(CH₃)— Ia-460 

—N(CH₂CH₃)— Ia-461 

—N(CH₂CH₂CH₃)— Ia-462 

—N(CH₂CH₂CH₂CH₃)— Ia-463 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-464 

—N(C(H)(CH₃)₂)— Ia-465 

—N(CH₂C(H)(CH₃)₂)— Ia-466 

—N(C(CH₃)₃)— Ia-467 

—N(CH₃)— Ia-468 

—N(CH₂CH₃)— Ia-469 

—N(CH₂CH₂CH₃)— Ia-470 

—N(CH₂CH₂CH₂CH₃)— Ia-471 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-472 

—N(C(H)(CH₃)₂)— Ia-473 

—N(CH₂C(H)(CH₃)₂)— Ia-474 

—N(C(CH₃)₃)— Ia-475 

—N(CH₃)— Ia-476 

—N(CH₂CH₃)— Ia-477 

—N(CH₂CH₂CH₃)— Ia-478 

—N(CH₂CH₂CH₂CH₃)— Ia-479 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-480 

—N(C(H)(CH₃)₂)— Ia-481 

—N(CH₂C(H)(CH₃)₂)— Ia-482 

—N(C(CH₃)₃)— Ia-483 

—N(CH₃)— Ia-484 

—N(CH₂CH₃)— Ia-485 

—N(CH₂CH₂CH₃)— Ia-486 

—N(CH₂CH₂CH₂CH₃)— Ia-487 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-488 

—N(C(H)(CH₃)₂)— Ia-489 

—N(CH₂C(H)(CH₃)₂)— Ia-490 

—N(C(CH₃)₃)— Ia-491  —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₃)— Ia-492 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₃)— Ia-493  —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂CH₂CH₃)— Ia-494  —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₂CH₂CH₃)— Ia-495 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-496 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)₂)— Ia-497  —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂C(H)(CH₃)₂)— Ia-498  —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(CH₃)₃)— Ia-499 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₃)— Ia-500  —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₃)—Ia-501  —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₂CH₃)— Ia-502 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₂CH₂CH₃)— Ia-503  —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(H)(CH₃)(CH₂CH₃))— Ia-504  —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(H)(CH₃)₂)—Ia-505  —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂C(H)(CH₃)₂)— Ia-506 —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(CH₃)₃)— Ia-507 

—N(CH₃)— Ia-508 

—N(CH₂CH₃)— Ia-509 

—N(CH₂CH₂CH₃)— Ia-510 

—N(CH₂CH₂CH₂CH₃)— Ia-511 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-512 

—N(C(H)(CH₃)₂)— Ia-513 

—N(CH₂C(H)(CH₃)₂)— Ia-514 

—N(C(CH₃)₃)— Ia-515 

—N(CH₃)— Ia-516 

—N(CH₂CH₃)— Ia-517 

—N(CH₂CH₂CH₃)— Ia-518 

—N(CH₂CH₂CH₂CH₃)— Ia-519 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-520 

—N(C(H)(CH₃)₂)— Ia-521 

—N(CH₂C(H)(CH₃)₂)— Ia-522 

—N(C(CH₃)₃)— Ia-523  —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₃)— Ia-524 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ia-525 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₃)— Ia-526 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-527 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-528 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ia-529 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-530 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(CH₃)₃)— Ia-531  —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₃)— Ia-532  —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ia-533 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₃)— Ia-534  —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ia-535  —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ia-536  —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ia-537 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-538  —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(CH₃)₃)— Ia-539 

—N(CH₃)— Ia-540 

—N(CH₂CH₃)— Ia-541 

—N(CH₂CH₂CH₃)— Ia-542 

—N(CH₂CH₂CH₂CH₃)— Ia-543 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-544 

—N(C(H)(CH₃)₂)— Ia-545 

—N(CH₂C(H)(CH₃)₂)— Ia-546 

—N(C(CH₃)₃)— Ia-547 

—N(CH₃)— Ia-548 

—N(CH₂CH₃)— Ia-549 

—N(CH₂CH₂CH₃)— Ia-550 

—N(CH₂CH₂CH₂CH₃)— Ia-551 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-552 

—N(C(H)(CH₃)₂)— Ia-553 

—N(CH₂C(H)(CH₃)₂)— Ia-554 

—N(C(CH₃)₃)— Ia-555 

—N(CH₃)— Ia-556 

—N(CH₂CH₃)— Ia-557 

—N(CH₂CH₂CH₃)— Ia-558 

—N(CH₂CH₂CH₂CH₃)— Ia-559 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-560 

—N(C(H)(CH₃)₂)— Ia-561 

—N(CH₂C(H)(CH₃)₂)— Ia-562 

—N(C(CH₃)₃)— Ia-563 

—N(CH₃)— Ia-564 

—N(CH₂CH₃)— Ia-565 

—N(CH₂CH₂CH₃)— Ia-566 

—N(CH₂CH₂CH₂CH₃)— Ia-567 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-568 

—N(C(H)(CH₃)₂)— Ia-569 

—N(CH₂C(H)(CH₃)₂)— Ia-570 

—N(C(CH₃)₃)— Ia-571 

—N(CH₃)— Ia-572 

—N(CH₂CH₃)— Ia-573 

—N(CH₂CH₂CH₃)— Ia-574 

—N(CH₂CH₂CH₂CH₃)— Ia-575 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-576 

—N(C(H)(CH₃)₂)— Ia-577 

—N(CH₂C(H)(CH₃)₂)— Ia-578 

—N(C(CH₃)₃)— Ia-579 

—N(CH₃)— Ia-580 

—N(CH₂CH₃)— Ia-581 

—N(CH₂CH₂CH₃)— Ia-582 

—N(CH₂CH₂CH₂CH₃)— Ia-583 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-584 

—N(C(H)(CH₃)₂)— Ia-585 

—N(CH₂C(H)(CH₃)₂)— Ia-586 

—N(C(CH₃)₃)— Ia-587 

—N(CH₃)— Ia-588 

—N(CH₂CH₃)— Ia-589 

—N(CH₂CH₂CH₃)— Ia-590 

—N(CH₂CH₂CH₂CH₃)— Ia-591 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-592 

—N(C(H)(CH₃)₂)— Ia-593 

—N(CH₂C(H)(CH₃)₂)— Ia-594 

—N(C(CH₃)₃)— Ia-595 

—N(CH₃)— Ia-596 

—N(CH₂CH₃)— Ia-597 

—N(CH₂CH₂CH₃)— Ia-598 

—N(CH₂CH₂CH₂CH₃)— Ia-599 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-600 

—N(C(H)(CH₃)₂)— Ia-601 

—N(CH₂C(H)(CH₃)₂)— Ia-602 

—N(C(CH₃)₃)— Ia-603 

—N(CH₃)— Ia-604 

—N(CH₂CH₃)— Ia-605 

—N(CH₂CH₂CH₃)— Ia-606 

—N(CH₂CH₂CH₂CH₃)— Ia-607 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-608 

—N(C(H)(CH₃)₂)— Ia-609 

—N(CH₂C(H)(CH₃)₂)— Ia-610 

—N(C(CH₃)₃)— Ia-611  —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₃)— Ia-612 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₃)— Ia-613 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ia-614 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ia-615 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ia-616 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ia-617 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ia-618 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(CH₃)₃)— Ia-619 

—N(CH₃)— Ia-620 

—N(CH₂CH₃)— Ia-621 

—N(CH₂CH₂CH₃)— Ia-622 

—N(CH₂CH₂CH₂CH₃)— Ia-623 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-624 

—N(C(H)(CH₃)₂)— Ia-625 

—N(CH₂C(H)(CH₃)₂)— Ia-626 

—N(C(CH₃)₃)— Ia-627 

—N(CH₃)— Ia-628 

—N(CH₂CH₃)— Ia-629 

—N(CH₂CH₂CH₃)— Ia-630 

—N(CH₂CH₂CH₂CH₃)— Ia-631 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-632 

—N(C(H)(CH₃)₂)— Ia-633 

—N(CH₂C(H)(CH₃)₂)— Ia-634 

—N(C(CH₃)₃)— Ia-635 

—N(CH₃)— Ia-636 

—N(CH₂CH₃)— Ia-637 

—N(CH₂CH₂CH₃)— Ia-638 

—N(CH₂CH₂CH₂CH₃)— Ia-639 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-640 

—N(C(H)(CH₃)₂)— Ia-641 

—N(CH₂C(H)(CH₃)₂)— Ia-642 

—N(C(CH₃)₃)— Ia-643 

—N(CH₃)— Ia-644 

—N(CH₂CH₃)— Ia-645 

—N(CH₂CH₂CH₃)— Ia-646 

—N(CH₂CH₂CH₂CH₃)— Ia-647 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-648 

—N(C(H)(CH₃)₂)— Ia-649 

—N(CH₂C(H)(CH₃)₂)— Ia-650 

—N(C(CH₃)₃)— Ia-651 

—N(CH₃)— Ia-652 

—N(CH₂CH₃)— Ia-653 

—N(CH₂CH₂CH₃)— Ia-654 

—N(CH₂CH₂CH₂CH₃)— Ia-655 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-656 

—N(C(H)(CH₃)₂)— Ia-657 

—N(CH₂C(H)(CH₃)₂)— Ia-658 

—N(C(CH₃)₃)— Ia-659 

—N(CH₃)— Ia-660 

—N(CH₂CH₃)— Ia-661 

—N(CH₂CH₂CH₃)— Ia-662 

—N(CH₂CH₂CH₂CH₃)— Ia-663 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-664 

—N(C(H)(CH₃)₂)— Ia-665 

—N(CH₂C(H)(CH₃)₂)— Ia-666 

—N(C(CH₃)₃)— Ia-667 

—N(CH₃)₃)— Ia-668 

—N(CH₂CH₃)— Ia-669 

—N(CH₂CH₂CH₃)— Ia-670 

—N(CH₂CH₂CH₂CH₃)— Ia-671 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-672 

—N(C(H)(CH₃)₂)— Ia-673 

—N(CH₂C(H)(CH₃)₂)— Ia-674 

—N(C(CH₃)₃)— Ia-675 

—N(CH₃)— Ia-676 

—N(CH₂CH₃)— Ia-677 

—N(CH₂CH₂CH₃)— Ia-678 

—N(CH₂CH₂CH₂CH₃)— Ia-679 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-680 

—N(C(H)(CH₃)₂)— Ia-681 

—N(CH₂C(H)(CH₃)₂)— Ia-682 

—N(C(CH₃)₃)— Ia-683 

—N(CH₃)— Ia-684 

—N(CH₂CH₃)— Ia-685 

—N(CH₂CH₂CH₃)— Ia-686 

—N(CH₂CH₂CH₂CH₃)— Ia-687 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-688 

—N(C(H)(CH₃)₂)— Ia-689 

—N(CH₂C(H)(CH₃)₂)— Ia-690 

—N(C(CH₃)₃)— Ia-691 

—N(CH₃)— Ia-692 

—N(CH₂CH₃)— Ia-693 

—N(CH₂CH₂CH₃)— Ia-694 

—N(CH₂CH₂CH₂CH₃)— Ia-695 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-696 

—N(C(H)(CH₃)₂)— Ia-697 

—N(CH₂C(H)(CH₃)₂)— Ia-698 

—N(C(CH₃)₃)— Ia-699 

—N(CH₃)— Ia-700 

—N(CH₂CH₃)— Ia-701 

—N(CH₂CH₂CH₃)— Ia-702 

—N(CH₂CH₂CH₂CH₃)— Ia-703 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-704 

—N(C(H)(CH₃)₂)— Ia-705 

—N(CH₂C(H)(CH₃)₂)— Ia-706 

—N(C(CH₃)₃)— Ia-707 

—N(CH₃)— Ia-708 

—N(CH₂CH₃)— Ia-709 

—N(CH₂CH₂CH₃)— Ia-710 

—N(CH₂CH₂CH₂CH₃)— Ia-711 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-712 

—N(C(H)(CH₃)₂)— Ia-713 

—N(CH₂C(H)(CH₃)₂)— Ia-714 

—N(C(CH₃)₃)— Ia-715 

—N(CH₃)— Ia-716 

—N(CH₂CH₃)— Ia-717 

—N(CH₂CH₂CH₃)— Ia-718 

—N(CH₂CH₂CH₂CH₃)— Ia-719 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-720 

—N(C(H)(CH₃)₂)— Ia-721 

—N(CH₂C(H)(CH₃)₂)— Ia-722 

—N(C(CH₃)₃)— Ia-723 

—N(CH₃)— Ia-724 

—N(CH₂CH₃)— Ia-725 

—N(CH₂CH₂CH₃)— Ia-726 

—N(CH₂CH₂CH₂CH₃)— Ia-727 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-728 

—N(C(H)(CH₃)₂)— Ia-729 

—N(CH₂C(H)(CH₃)₂)— Ia-730 

—N(C(CH₃)₃)— Ia-731 

—N(CH₃)— Ia-732 

—N(CH₂CH₃)— Ia-733 

—N(CH₂CH₂CH₃)— Ia-734 

—N(CH₂CH₂CH₂CH₃)— Ia-735 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-736 

—N(C(H)(CH₃)₂)— Ia-737 

—N(CH₂C(H)(CH₃)₂)— Ia-738 

—N(C(CH₃)₃)— Ia-739 

—N(CH₃)— Ia-740 

—N(CH₂CH₃)— Ia-741 

—N(CH₂CH₂CH₃)— Ia-742 

—N(CH₂CH₂CH₂CH₃)— Ia-743 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-744 

—N(C(H)(CH₃)₂)— Ia-745 

—N(CH₂C(H)(CH₃)₂)— Ia-746 

—N(C(CH₃)₃)— Ia-747 

—N(CH₃)— Ia-748 

—N(CH₂CH₃)— Ia-749 

—N(CH₂CH₂CH₃)— Ia-750 

—N(CH₂CH₂CH₂CH₃)— Ia-751 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-752 

—N(C(H)(CH₃)₂)— Ia-753 

—N(CH₂C(H)(CH₃)₂)— Ia-754 

—N(C(CH₃)₃)— Ia-755 

—N(CH₃)— Ia-756 

—N(CH₂CH₃)— Ia-757 

—N(CH₂CH₂CH₃)— Ia-758 

—N(CH₂CH₂CH₂CH₃)— Ia-759 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-760 

—N(C(H)(CH₃)₂)— Ia-761 

—N(CH₂C(H)(CH₃)₂)— Ia-762 

—N(C(CH₃)₃)— Ia-763 

—N(CH₃)— Ia-764 

—N(CH₂CH₃)— Ia-765 

—N(CH₂CH₂CH₃)— Ia-766 

—N(CH₂CH₂CH₂CH₃)— Ia-767 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-768 

—N(C(H)(CH₃)₂)— Ia-769 

—N(CH₂C(H)(CH₃)₂)— Ia-770 

—N(C(CH₃)₃)— Ia-771 

—N(CH₃)— Ia-772 

—N(CH₂CH₃)— Ia-773 

—N(CH₂CH₂CH₃)— Ia-774 

—N(CH₂CH₂CH₂CH₃)— Ia-775 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-776 

—N(C(H)(CH₃)₂)— Ia-777 

—N(CH₂C(H)(CH₃)₂)— Ia-778 

—N(C(CH₃)₃)— Ia-779  —CH₂—NH—CH₃ —N(CH₃)— Ia-780  —CH₂—NH—CH₃—N(CH₂CH₃)— Ia-781  —CH₂—NH—CH₃ —N(CH₂CH₂CH₃)— Ia-782  —CH₂—NH—CH₃—N(CH₂CH₂CH₂CH₃)— Ia-783  —CH₂—NH—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ia-784 —CH₂—NH—CH₃ —N(C(H)(CH₃)₂)— Ia-785  —CH₂—NH—CH₃ —N(CH₂C(H)(CH₃)₂)—Ia-786  —CH₂—NH—CH₃ —N(C(CH₃)₃)— Ia-787  —CH₂—NH—CH₂—CH₃ —N(CH₃)—Ia-788  —CH₂—NH—CH₂—CH₃ —N(CH₂CH₃)— Ia-789  —CH₂—NH—CH₂—CH₃—N(CH₂CH₂CH₃)— Ia-790  —CH₂—NH—CH₂—CH₃ —N(CH₂CH₂CH₂CH₃)— Ia-791 —CH₂—NH—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ia-792  —CH₂—NH—CH₂—CH₃—N(C(H)(CH₃)₂)— Ia-793  —CH₂—NH—CH₂—CH₃ —N(CH₂C(H)(CH₃)₂)— Ia-794 —CH₂—NH—CH₂—CH₃ —N(C(CH₃)₃)— Ia-795  —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₃)—Ia-796  —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₃)— Ia-797  —CH₂—NH—CH₂—CH₂—CH₃—N(CH₂CH₂CH₃)— Ia-798  —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₂CH₂CH₃)— Ia-799 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ia-800  —CH₂—NH—CH₂—CH₂—CH₃—N(C(H)(CH₃)₂)— Ia-801  —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂C(H)(CH₃)₂)— Ia-802 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(CH₃)₃)— Ia-803 

—N(CH₃)— Ia-804 

—N(CH₂CH₃)— Ia-805 

—N(CH₂CH₂CH₃)— Ia-806 

—N(CH₂CH₂CH₂CH₃)— Ia-807 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-808 

—N(C(H)(CH₃)₂)— Ia-809 

—N(CH₂C(H)(CH₃)₂)— Ia-810 

—N(C(CH₃)₃)— Ia-811 

—N(CH₃)— Ia-812 

—N(CH₂CH₃)— Ia-813 

—N(CH₂CH₂CH₃)— Ia-814 

—N(CH₂CH₂CH₂CH₃)— Ia-815 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-816 

—N(C(H)(CH₃)₂)— Ia-817 

—N(CH₂C(H)(CH₃)₂)— Ia-818 

—N(C(CH₃)₃)— Ia-819 

—N(CH₃)— Ia-820 

—N(CH₂CH₃)— Ia-821 

—N(CH₂CH₂CH₃)— Ia-822 

—N(CH₂CH₂CH₂CH₃)— Ia-823 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-824 

—N(C(H)(CH₃)₂)— Ia-825 

—N(CH₂C(H)(CH₃)₂)— Ia-826 

—N(C(CH₃)₃)— Ia-827 

—N(CH₃)— Ia-828 

—N(CH₂CH₃)— Ia-829 

—N(CH₂CH₂CH₃)— Ia-830 

—N(CH₂CH₂CH₂CH₃)— Ia-831 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-832 

—N(C(H)(CH₃)₂)— Ia-833 

—N(CH₂C(H)(CH₃)₂)— Ia-834 

—N(C(CH₃)₃)— Ia-835 

—N(CH₃)— Ia-836 

—N(CH₂CH₃)— Ia-837 

—N(CH₂CH₂CH₃)— Ia-838 

—N(CH₂CH₂CH₂CH₃)— Ia-839 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-840 

—N(C(H)(CH₃)₂)— Ia-841 

—N(CH₂C(H)(CH₃)₂)— Ia-842 

—N(C(CH₃)₂)— Ia-843 

—N(CH₃)— Ia-844 

—N(CH₂CH₃)— Ia-845 

—N(CH₂CH₂CH₃)— Ia-846 

—N(CH₂CH₂CH₂CH₃)— Ia-847 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-848 

—N(C(H)(CH₃)₂)— Ia-849 

—N(CH₂C(H)(CH₃)₂)— Ia-850 

—N(C(CH₃)₃)— Ia-851 

—N(CH₃)— Ia-852 

—N(CH₂CH₃)— Ia-853 

—N(CH₂CH₂CH₃)— Ia-854 

—N(CH₂CH₂CH₂CH₃)— Ia-855 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-856 

—N(C(H)(CH₃)₂)— Ia-857 

—N(CH₂C(H)(CH₃)₂)— Ia-858 

—N(C(CH₃)₃)— Ia-859 

—N(CH₃)— Ia-860 

—N(CH₂CH₃)— Ia-861 

—N(CH₂CH₂CH₃)— Ia-862 

—N(CH₂CH₂CH₂CH₃)— Ia-863 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-864 

—N(C(H)(CH₃)₂)— Ia-865 

—N(CH₂C(H)(CH₃)₂)— Ia-866 

—N(C(CH₃)₃)— Ia-867 

—N(CH₃)— Ia-868 

—N(CH₂CH₃)— Ia-869 

—N(CH₂CH₂CH₃)— Ia-870 

—N(CH₂CH₂CH₂CH₃)— Ia-871 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-872 

—N(C(H)(CH₃)₂)— Ia-873 

—N(CH₂C(H)(CH₃)₂)— Ia-874 

—N(C(CH₃)₃)— Ia-875 

—N(CH₃)— Ia-876 

—N(CH₂CH₃)— Ia-877 

—N(CH₂CH₂CH₃)— Ia-878 

—N(CH₂CH₂CH₂CH₃)— Ia-879 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-880 

—N(C(H)(CH₃)₂)— Ia-881 

—N(CH₂C(H)(CH₃)₂)— Ia-882 

—N(C(CH₃)₃)— Ia-883 

—N(CH₃)— Ia-884 

—N(CH₂CH₃)— Ia-885 

—N(CH₂CH₂CH₃)— Ia-886 

—N(CH₂CH₂CH₂CH₃)— Ia-887 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-888 

—N(C(H)(CH₃)₂)— Ia-889 

—N(CH₂C(H)(CH₃)₂)— Ia-890 

—N(C(CH₃)₃)— Ia-891 

—N(CH₃)— Ia-892 

—N(CH₂CH₃)— Ia-893 

—N(CH₂CH₂CH₃)— Ia-894 

—N(CH₂CH₂CH₂CH₃)— Ia-895 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-896 

—N(C(H)(CH₃)₂)— Ia-897 

—N(CH₂C(H)(CH₃)₂)— Ia-898 

—N(C(CH₃)₃)— Ia-899 

—N(CH₃)— Ia-900 

—N(CH₂CH₃)— Ia-901 

—N(CH₂CH₂CH₃)— Ia-902 

—N(CH₂CH₂CH₂CH₃)— Ia-903 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-904 

—N(C(H)(CH₃)₂)— Ia-905 

—N(CH₂C(H)(CH₃)₂)— Ia-906 

—N(C(CH₃)₃)— Ia-907 

—N(CH₃)— Ia-908 

—N(CH₂CH₃)— Ia-909 

—N(CH₂CH₂CH₃)— Ia-910 

—N(CH₂CH₂CH₂CH₃)— Ia-911 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-912 

—N(C(H)(CH₃)₂)— Ia-913 

—N(CH₂C(H)(CH₃)₂)— Ia-914 

—N(C(CH₃)₃)— Ia-915 

—N(CH₃)— Ia-916 

—N(CH₂CH₃)— Ia-917 

—N(CH₂CH₂CH₃)— Ia-918 

—N(CH₂CH₂CH₂CH₃)— Ia-919 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-920 

—N(C(H)(CH₃)₂)— Ia-921 

—N(CH₂C(H)(CH₃)₂)— Ia-922 

—N(C(CH₃)₃)— Ia-923 

—N(CH₃)— Ia-924 

—N(CH₂CH₃)— Ia-925 

—N(CH₂CH₂CH₃)— Ia-926 

—N(CH₂CH₂CH₂CH₃)— Ia-927 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-928 

—N(C(H)(CH₃)₂)— Ia-929 

—N(CH₂C(H)(CH₃)₂)— Ia-930 

—N(C(CH₃)₃)— Ia-931 

—N(CH₃)— Ia-932 

—N(CH₂CH₃)— Ia-933 

—N(CH₂CH₂CH₃)— Ia-934 

—N(CH₂CH₂CH₂CH₃)— Ia-935 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-936 

—N(C(H)(CH₃)₂)— Ia-937 

—N(CH₂C(H)(CH₃)₂)— Ia-938 

—N(C(CH₃)₃)— Ia-939 

—N(CH₃)— Ia-940 

—N(CH₂CH₃)— Ia-941 

—N(CH₂CH₂CH₃)— Ia-942 

—N(CH₂CH₂CH₂CH₃)— Ia-943 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-944 

—N(C(H)(CH₃)₂)— Ia-945 

—N(CH₂C(H)(CH₃)₂)— Ia-946 

—N(C(CH₃)₃)— Ia-947 

—N(CH₃)— Ia-948 

—N(CH₂CH₃)— Ia-949 

—N(CH₂CH₂CH₃)— Ia-950 

—N(CH₂CH₂CH₂CH₃)— Ia-951 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-952 

—N(C(H)(CH₃)₂)— Ia-953 

—N(CH₂C(H)(CH₃)₂)— Ia-954 

—N(C(CH₃)₃)— Ia-955 

—N(CH₃)— Ia-956 

—N(CH₂CH₃)— Ia-957 

—N(CH₂CH₂CH₃)— Ia-958 

—N(CH₂CH₂CH₂CH₃)— Ia-959 

—N(C(H)(CH₃)(CH₂CH₃))— Ia-960 

—N(C(H)(CH₃)₂)— Ia-961 

—N(CH₂C(H)(CH₃)₂)— Ia-962 

—N(C(CH₃)₃)— Ia-963  —CH₂—N(CH₂CH₃)(CH₃) —N(CH₃)— Ia-964 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ia-965  —CH₂—N(CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ia-966  —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ia-967 —CH₂—N(CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ia-968  —CH₂—N(CH₂CH₃)(CH₃)—N(C(H)(CH₃)₂)— Ia-969  —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ia-970 —CH₂—N(CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ia-971  —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₃)—Ia-972  —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ia-973 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₃)— Ia-974  —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(CH₂CH₂CH₂CH₃)— Ia-975  —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))—Ia-976  —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ia-977 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ia-978  —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(C(CH₃)₃)— Ia-979  —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₃)— Ia-980 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ia-981  —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ia-982  —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)—Ia-983  —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ia-984 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ia-985 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ia-986 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ia-987  —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₃)— Ia-988  —CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₃)— Ia-989 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₂CH₃)— Ia-990  —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₂CH₂CH₂CH₃)— Ia-991  —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ia-992  —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)₂)— Ia-993 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂C(H)(CH₃)₂)— Ia-994  —CH₂—NH—CH₂CH₂CH₂CH₃—N(C(CH₃)₃)— Ia-995  —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₃)— Ia-996 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₃)— Ia-997  —CH₂—NH—CH₂CH₂—O—CH₃—N(CH₂CH₂CH₃)— Ia-998  —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₂CH₂CH₃)— Ia-999 —CH₂—NH—CH₂CH₂—O—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ia-1000 —CH₂—NH—CH₂CH₂—O—CH₃—N(C(H)(CH₃)₂)— Ia-1001 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂C(H)(CH₃)₂)— Ia-1002—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(CH₃)₃)— Ia-1003

—N(CH₃)— Ia-1004

—N(CH₂CH₃)— Ia-1005

—N(CH₂CH₂CH₃)— Ia-1006

—N(CH₂CH₂CH₂CH₃)— Ia-1007

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1008

—N(C(H)(CH₃)₂)— Ia-1009

—N(CH₂C(H)(CH₃)₂)— Ia-1010

—N(C(CH₃)₃)— Ia-1011

—N(CH₃)— Ia-1012

—N(CH₂CH₃)— Ia-1013

—N(CH₂CH₂CH₃)— Ia-1014

—N(CH₂CH₂CH₂CH₃)— Ia-1015

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1016

—N(C(H)(CH₃)₂)— Ia-1017

—N(CH₂C(H)(CH₃)₂)— Ia-1018

—N(C(CH₃)₃)— Ia-1019

—N(CH₃)— Ia-1020

—N(CH₂CH₃)— Ia-1021

—N(CH₂CH₂CH₃)— Ia-1022

—N(CH₂CH₂CH₂CH₃)— Ia-1023

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1024

—N(C(H)(CH₃)₂)— Ia-1025

—N(CH₂C(H)(CH₃)₂)— Ia-1026

—N(C(CH₃)₃)— Ia-1027

—N(CH₃)— Ia-1028

—N(CH₂CH₃)— Ia-1029

—N(CH₂CH₂CH₃)— Ia-1030

—N(CH₂CH₂CH₂CH₃)— Ia-1031

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1032

—N(C(H)(CH₃)₂)— Ia-1033

—N(CH₂C(H)(CH₃)₂)— Ia-1034

—N(C(CH₃)₃)— Ia-1035

—N(CH₃)— Ia-1036

—N(CH₂CH₃)— Ia-1037

—N(CH₂CH₂CH₃)— Ia-1038

—N(CH₂CH₂CH₂CH₃)— Ia-1039

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1040

—N(C(H)(CH₃)₂)— Ia-1041

—N(CH₂C(H)(CH₃)₂)— Ia-1042

—N(C(CH₃)₃)— Ia-1043

—N(CH₃)— Ia-1044

—N(CH₂CH₃)— Ia-1045

—N(CH₂CH₂CH₃)— Ia-1046

—N(CH₂CH₂CH₂CH₃)— Ia-1047

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1048

—N(C(H)(CH₃)₂)— Ia-1049

—N(CH₂C(H)(CH₃)₂)— Ia-1050

—N(C(CH₃)₃)— Ia-1051

—N(CH₃)— Ia-1052

—N(CH₂CH₃)— Ia-1053

—N(CH₂CH₂CH₃)— Ia-1054

—N(CH₂CH₂CH₂CH₃)— Ia-1055

—N(C(H)(CH₃)(CH₂CH₃))— Ia-1056

—N(C(H)(CH₃)₂)— Ia-1057

—N(CH₂C(H)(CH₃)₂)— Ia-1058

—N(C(CH₃)₃)— Compound n —R¹ X Ia-a1  1 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)—Ia-a2  2 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ia-a3  3 —(CH₂)_(n)—N(CH₃)₂—CH(OH)— Ia-a4  4 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ia-a5  5—(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ia-a6  6 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ia-a7 1 —(CH₂)_(n)—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a8  2—(CH₂)_(n)—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a9  3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a10  4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a11  5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a12  6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a13  1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a14  2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a15  3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a16  4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a17  5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a18  6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a19  1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a20  2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a21  3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a22  4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a23  5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a24  6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a25  1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a26  2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a27  3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a28  4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a29  5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a30  6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a31  1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ia-a32  2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a33  3—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a34  4 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ia-a35  5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a36  6—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a37  1 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ia-a38  2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a39  3—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a40  4 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ia-a41  5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a42  6—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a43  1 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ia-a44  2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a45 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a46  4 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ia-a47  5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a48 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a49  1

—CH(OH)— Ia-a50  2

—CH(OH)— Ia-a51  3

—CH(OH)— Ia-a52  4

—CH(OH)— Ia-a53  5

—CH(OH)— Ia-a54  6

—CH(OH)— Ia-a55  1

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a56  2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a57  3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a58  4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a59  5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a60  6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a61  1

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a62  2

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a63  3

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a64  4

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a65  5

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a66  6

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a67  1

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a68  2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a69  3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a70  4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a71  5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a72  6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a73  1

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a74  2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a75  3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a76  4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a77  5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a78  6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a79  1

—N(CH₂—CH₂—OH)— Ia-a80  2

—N(CH₂—CH₂—OH)— Ia-a81  3

—N(CH₂—CH₂—OH)— Ia-a82  4

—N(CH₂—CH₂—OH)— Ia-a83  5

—N(CH₂—CH₂—OH)— Ia-a84  6

—N(CH₂—CH₂—OH)— Ia-a85  1

—N(CH₂—CH₂—F)— Ia-a86  2

—N(CH₂—CH₂—F)— Ia-a87  3

—N(CH₂—CH₂—F)— Ia-a88  4

—N(CH₂—CH₂—F)— Ia-a89  5

—N(CH₂—CH₂—F)— Ia-a90  6

—N(CH₂—CH₂—F)— Ia-a91  1

—N(CH₂—CH₂—OCH₃)— Ia-a92  2

—N(CH₂—CH₂—OCH₃)— Ia-a93  3

—N(CH₂—CH₂—OCH₃)— Ia-a94  4

—N(CH₂—CH₂—OCH₃)— Ia-a95  5

—N(CH₂—CH₂—OCH₃)— Ia-a96  6

—N(CH₂—CH₂—OCH₃)— Compound m —R¹ X Ia-a146 2 —O—(CH₂)_(m)—N(CH₃)₂—CH(OH)— Ia-a147 3 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ia-a148 4—O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ia-a149 5 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)—Ia-a150 6 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ia-a151 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a152 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a153 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a154 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a155 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a156 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a157 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a158 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a159 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a160 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a161 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a162 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a163 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a164 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a165 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a166 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a167 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a168 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a169 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a170 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a171 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ia-a172 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a173 4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a174 5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ia-a175 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ia-a176 2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a178 3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ia-a179 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a180 5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ia-a181 6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ia-a182 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a1833 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a184 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ia-a185 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)—Ia-a186 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ia-a187 2

—CH(OH)— Ia-a188 3

—CH(OH)— Ia-a189 4

—CH(OH)— Ia-a190 5

—CH(OH)— Ia-a191 6

—CH(OH)— Ia-a192 2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a193 3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a194 4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a195 5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a196 6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a197 2

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a198 3

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a199 4

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a200 5

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a201 6

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a202 2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a203 3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a204 4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a205 5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a206 6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a207 2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a208 3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a209 4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a210 5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a211 6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a212 2

—N(CH₂—CH₂—OH)— Ia-a213 3

—N(CH₂—CH₂—OH)— Ia-a214 4

—N(CH₂—CH₂—OH)— Ia-a215 5

—N(CH₂—CH₂—OH)— Ia-a216 6

—N(CH₂—CH₂—OH)— Ia-a217 2

—N(CH₂—CH₂—F)— Ia-a218 3

—N(CH₂—CH₂—F)— Ia-a219 4

—N(CH₂—CH₂—F)— Ia-a220 5

—N(CH₂—CH₂—F)— Ia-a221 6

—N(CH₂—CH₂—F)— Ia-a222 2

—N(CH₂—CH₂—OCH₃)— Ia-a223 3

—N(CH₂—CH₂—OCH₃)— Ia-a224 4

—N(CH₂—CH₂—OCH₃)— Ia-a225 5

—N(CH₂—CH₂—OCH₃)— Ia-a226 6

—N(CH₂—CH₂—OCH₃)— Compound —R¹ X Ia-a267 —CH₂—N(CH₂—CH₃)₂ —CH(OH)—Ia-a268 —CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a269—CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a270 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a271 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a275 —CH₂—N(CH₂—CH₂—CH₃)₂ —CH(OH)— Ia-a276—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a277—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a278—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a279—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a283—CH₂—N(CH₂—CH₂OH)₂ —CH(OH)— Ia-a284 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a285 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a286 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a291 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)—Ia-a292 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a293—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a294—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a295—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a296—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a297—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ia-a298—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a299—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)— Ia-a300—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a301—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a302—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a303—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a304—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a305—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ia-a306—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a307

—CH(OH)— Ia-a308

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a309

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a310

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a311

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a312

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a313

—N(C(O)N(H)—CH₂—CF₃)— Ia-a314

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a315

—CH(OH)— Ia-a316

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a317

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a318

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a319

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a320

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a321

—N(C(O)N(H)—CH₂—CF₃)— Ia-a322

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a323

—CH(OH)— Ia-a324

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a325

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a326

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a327

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a328

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a329

—N(C(O)N(H)—CH₂—CF₃)— Ia-a330

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a331

—CH(OH)— Ia-a332

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a333

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a334

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a335

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a336

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a337

—N(C(O)N(H)—CH₂—CF₃)— Ia-a338

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a339

—CH(OH)— Ia-a340

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a341

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a342

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a343

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a344

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a345

—N(C(O)N(H)—CH₂—CF₃)— Ia-a346

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a347

—CH(OH)— Ia-a348

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a349

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a350

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a351

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a352

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a353

—N(C(O)N(H)—CH₂—CF₃)— Ia-a354

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a355

—CH(OH)— Ia-a356

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a357

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a358

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a359

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a360

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a361

—N(C(O)N(H)—CH₂—CF₃)— Ia-a362

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a363

—CH(OH)— Ia-a364

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a365

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a366

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a367

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a368

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a369

—N(C(O)N(H)—CH₂—CF₃)— Ia-a370

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a371

—CH(OH)— Ia-a372

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a373

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a374

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a375

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a376

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a377

—N(C(O)N(H)—CH₂—CF₃)— Ia-a378

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a379

—CH(OH)— Ia-a380

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a381

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a382

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a383

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a384

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a385

—N(C(O)N(H)—CH₂—CF₃)— Ia-a386

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a387

—CH(OH)— Ia-a388

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a389

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a390

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a391

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a392

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a393

—N(C(O)N(H)—CH₂—CF₃)— Ia-a394

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a395

—CH(OH)— Ia-a396

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a397

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a398

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a399

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a400

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a401

—N(C(O)N(H)—CH₂—CF₃)— Ia-a402

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a403

—CH(OH)— Ia-a404

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a405

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a406

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a407

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a408

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a409

—N(C(O)N(H)—CH₂—CF₃)— Ia-a410

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a411

—CH(OH)— Ia-a412

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a413

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a414

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a415

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a416

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a417

—N(C(O)N(H)—CH₂—CF₃)— Ia-a418

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a419

—CH(OH)— Ia-a420

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a421

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a422

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a423

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a424

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a425

—N(C(O)N(H)—CH₂—CF₃)— Ia-a426

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a427

—CH(OH)— Ia-a428

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a429

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a430

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a431

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a432

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a433

—N(C(O)N(H)—CH₂—CF₃)— Ia-a434

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a435

—CH(OH)— Ia-a436

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a437

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a438

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a439

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a440

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a441

—N(C(O)N(H)—CH₂—CF₃)— Ia-a442

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a443

—CH(OH)— Ia-a444

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a445

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a446

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a447

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a448

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a449

—N(C(O)N(H)—CH₂—CF₃)— Ia-a450

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a451

—CH(OH)— Ia-a452

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a453

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a454

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a455

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a456

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a457

—N(C(O)N(H)—CH₂—CF₃)— Ia-a458

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a459

—CH(OH)— Ia-a460

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a461

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a462

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a463

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a464

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a465

—N(C(O)N(H)—CH₂—CF₃)— Ia-a466

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a467

—CH(OH)— Ia-a468

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a469

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a470

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a471

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a472

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a473

—N(C(O)N(H)—CH₂—CF₃)— Ia-a474

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a475

—CH(OH)— Ia-a476

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a477

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a478

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a479

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a480

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a481

—N(C(O)N(H)—CH₂—CF₃)— Ia-a482

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a483

—CH(OH)— Ia-a484

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a485

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a486

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a487

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a488

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a489

—N(C(O)N(H)—CH₂—CF₃)— Ia-a490

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a491 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —CH(OH)— Ia-a492—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a493—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a494—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a495—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a496—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a497—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CF₃)— Ia-a498—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a499—CH₂—CH₂—CH₂—OS(O)₂OH —CH(OH)— Ia-a500 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a501 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a502 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a503 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a504 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a505 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CF₃)— Ia-a506 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a507

—CH(OH)— Ia-a508

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a509

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a510

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a511

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a512

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a513

—N(C(O)N(H)—CH₂—CF₃)— Ia-a514

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a515

—CH(OH)— Ia-a516

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a517

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a518

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a519

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a520

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a521

—N(C(O)N(H)—CH₂—CF₃)— Ia-a522

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a523 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)—Ia-a524 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a525—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a526—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a527—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a528—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a529—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ia-a530—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a531—CH₂—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)— Ia-a532 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a533 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a534 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a535 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a536 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a537 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CF₃)— Ia-a538 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a539

—CH(OH)— Ia-a540

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a541

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a542

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a543

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a544

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a545

—N(C(O)N(H)—CH₂—CF₃)— Ia-a546

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a547

—CH(OH)— Ia-a548

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a549

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a550

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a551

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a552

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a553

—N(C(O)N(H)—CH₂—CF₃)— Ia-a554

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a555

—CH(OH)— Ia-a556

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a557

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a558

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a559

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a560

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a561

—N(C(O)N(H)—CH₂—CF₃)— Ia-a562

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a563

—CH(OH)— Ia-a564

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a565

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a566

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a567

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a568

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a569

—N(C(O)N(H)—CH₂—CF₃)— Ia-a570

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a571

—CH(OH)— Ia-a572

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a573

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a574

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a575

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a576

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a577

—N(C(O)N(H)—CH₂—CF₃)— Ia-a578

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a579

—CH(OH)— Ia-a580

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a581

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a582

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a583

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a584

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a585

—N(C(O)N(H)—CH₂—CF₃)— Ia-a586

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a587

—CH(OH)— Ia-a588

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a589

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a590

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a591

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a592

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a593

—N(C(O)N(H)—CH₂—CF₃)— Ia-a594

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a595

—CH(OH)— Ia-a596

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a597

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a598

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a599

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a600

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a601

—N(C(O)N(H)—CH₂—CF₃)— Ia-a602

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a603

—CH(OH)— Ia-a604

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a605

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a606

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a607

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a608

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a609

—N(C(O)N(H)—CH₂—CF₃)— Ia-a610

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a611 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —CH(OH)—Ia-a612 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a613—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a614—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a615—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a616—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a617—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ia-a618—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a619

—CH(OH)— Ia-a620

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a621

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a622

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a623

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a624

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a625

—N(C(O)N(H)—CH₂—CF₃)— Ia-a626

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a627

—CH(OH)— Ia-a628

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a629

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a630

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a631

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a632

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a633

—N(C(O)N(H)—CH₂—CF₃)— Ia-a634

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a635

—CH(OH)— Ia-a636

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a637

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a638

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a639

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a640

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a641

—N(C(O)N(H)—CH₂—CF₃)— Ia-a642

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a643

—CH(OH)— Ia-a644

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a645

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a646

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a647

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a648

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a649

—N(C(O)N(H)—CH₂—CF₃)— Ia-a650

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a651

—CH(OH)— Ia-a652

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a653

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a654

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a655

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a656

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a657

—N(C(O)N(H)—CH₂—CF₃)— Ia-a658

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a659

—CH(OH)— Ia-a660

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a661

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a662

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a663

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a664

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a665

—N(C(O)N(H)—CH₂—CF₃)— Ia-a666

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a667

—CH(OH)— Ia-a668

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a669

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a670

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a671

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a672

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a673

—N(C(O)N(H)—CH₂—CF₃)— Ia-a674

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a675

—CH(OH)— Ia-a676

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a677

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a678

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a679

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a680

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a681

—N(C(O)N(H)—CH₂—CF₃)— Ia-a682

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a683

—CH(OH)— Ia-a684

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a685

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a686

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a687

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a688

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a689

—N(C(O)N(H)—CH₂—CF₃)— Ia-a690

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a691

—CH(OH)— Ia-a692

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a693

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a694

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a695

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a696

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a697

—N(C(O)N(H)—CH₂—CF₃)— Ia-a698

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a699

—CH(OH)— Ia-a700

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a701

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a702

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a703

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a704

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a705

—N(C(O)N(H)—CH₂—CF₃)— Ia-a706

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a707

—CH(OH)— Ia-a708

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a709

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a710

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a711

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a712

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a713

—N(C(O)N(H)—CH₂—CF₃)— Ia-a714

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a715

—CH(OH)— Ia-a716

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a717

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a718

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a719

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a720

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a721

—N(C(O)N(H)—CH₂—CF₃)— Ia-a722

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a723

—CH(OH)— Ia-a724

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a725

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a726

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a727

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a728

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a729

—N(C(O)N(H)—CH₂—CF₃)— Ia-a730

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a731

—CH(OH)— Ia-a732

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a733

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a734

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a735

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a736

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a737

—N(C(O)N(H)—CH₂—CF₃)— Ia-a738

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a739

—CH(OH)— Ia-a740

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a741

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a742

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a743

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a744

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a745

—N(C(O)N(H)—CH₂—CF₃)— Ia-a746

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a747

—CH(OH)— Ia-a748

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a749

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a750

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a751

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a752

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a753

—N(C(O)N(H)—CH₂—CF₃)— Ia-a754

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a755

—CH(OH)— Ia-a756

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a757

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a758

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a759

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a760

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a761

—N(C(O)N(H)—CH₂—CF₃)— Ia-a762

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a763

—CH(OH)— Ia-a764

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a765

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a766

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a767

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a768

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a769

—N(C(O)N(H)—CH₂—CF₃)— Ia-a770

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a771

—CH(OH)— Ia-a772

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a773

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a774

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a775

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a776

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a777

—N(C(O)N(H)—CH₂—CF₃)— Ia-a778

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a779 —CH₂—NH—CH₃ —CH(OH)— Ia-a780 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a781 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)—Ia-a782 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a783 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a784 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)—Ia-a785 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ia-a786 —CH₂—NH—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a787 —CH₂—NH—CH₂—CH₃ —CH(OH)— Ia-a788—CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a789 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a790 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a791 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a792 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a793 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CF₃)—Ia-a794 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a795—CH₂—NH—CH₂—CH₂—CH₃ —CH(OH)— Ia-a796 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a797 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a798 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a799 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a800 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a801 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CF₃)— Ia-a802 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a803

—CH(OH)— Ia-a804

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a805

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a806

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a807

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a808

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a809

—N(C(O)N(H)—CH₂—CF₃)— Ia-a810

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a811

—CH(OH)— Ia-a812

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a813

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a814

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a815

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a816

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a817

—N(C(O)N(H)—CH₂—CF₃)— Ia-a818

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a819

—CH(OH)— Ia-a820

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a821

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a822

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a823

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a824

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a825

—N(C(O)N(H)—CH₂—CF₃)— Ia-a826

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a827

—CH(OH)— Ia-a828

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a829

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a830

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a831

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a832

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a833

—N(C(O)N(H)—CH₂—CF₃)— Ia-a834

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a835

—CH(OH)— Ia-a836

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a837

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a838

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a839

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a840

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a841

—N(C(O)N(H)—CH₂—CF₃)— Ia-a842

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a843

—CH(OH)— Ia-a844

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a845

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a846

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a847

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a848

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a849

—N(C(O)N(H)—CH₂—CF₃)— Ia-a850

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a851

—CH(OH)— Ia-a852

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a853

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a854

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a855

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a856

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a857

—N(C(O)N(H)—CH₂—CF₃)— Ia-a858

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a859

—CH(OH)— Ia-a860

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a861

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a862

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a863

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a864

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a865

—N(C(O)N(H)—CH₂—CF₃)— Ia-a866

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a867

—CH(OH)— Ia-a868

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a869

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a870

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a871

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a872

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a873

—N(C(O)N(H)—CH₂—CF₃)— Ia-a874

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a875

—CH(OH)— Ia-a876

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a877

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a878

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a879

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a880

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a881

—N(C(O)N(H)—CH₂—CF₃)— Ia-a882

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a883

—CH(OH)— Ia-a884

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a885

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a886

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a887

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a888

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a889

—N(C(O)N(H)—CH₂—CF₃)— Ia-a890

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a891

—CH(OH)— Ia-a892

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a893

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a894

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a895

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a896

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a897

—N(C(O)N(H)—CH₂—CF₃)— Ia-a898

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a899

—CH(OH)— Ia-a900

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a901

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a902

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a903

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a904

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a905

—N(C(O)N(H)—CH₂—CF₃)— Ia-a906

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a907

—CH(OH)— Ia-a908

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a909

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a910

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a911

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a912

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a913

—N(C(O)N(H)—CH₂—CF₃)— Ia-a914

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a915

—CH(OH)— Ia-a916

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a917

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a918

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a919

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a920

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a921

—N(C(O)N(H)—CH₂—CF₃)— Ia-a922

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a923

—CH(OH)— Ia-a924

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a925

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a926

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a927

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a928

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a929

—N(C(O)N(H)—CH₂—CF₃)— Ia-a930

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a931

—CH(OH)— Ia-a932

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a933

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a934

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a935

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a936

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a937

—N(C(O)N(H)—CH₂—CF₃)— Ia-a938

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a939

—CH(OH)— Ia-a940

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a941

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a942

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a943

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a944

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a945

—N(C(O)N(H)—CH₂—CF₃)— Ia-a946

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a947

—CH(OH)— Ia-a948

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a949

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a950

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a951

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a952

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a953

—N(C(O)N(H)—CH₂—CF₃)— Ia-a954

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a955

—CH(OH)— Ia-a956

—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a957

—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a958

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a959

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a960

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a961

—N(C(O)N(H)—CH₂—CF₃)— Ia-a962

—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a963 —CH₂—N(CH₂CH₃)(CH₃) —CH(OH)— Ia-a964—CH₂—N(CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a965 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a966 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a967 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a968 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a969 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ia-a970 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a971 —CH₂—N(CH₂CH₂CH₃)(CH₃) —CH(OH)— Ia-a972—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a973—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a974—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a975—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a976—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a977—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CF₃)— Ia-a978—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—(CH₂)₃—OH)— Ia-a979—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —CH(OH)— Ia-a980 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a981 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ia-a982 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a983 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a984 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a985 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ia-a986 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a987 —CH₂—NH—CH₂CH₂CH₂CH₃ —CH(OH)— Ia-a988—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a989—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a990—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a991—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a992—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ia-a993—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ia-a994 —CH₂—NH—CH₂CH₂CH₂CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ia-a995 —CH₂—NH—CH₂CH₂—O—CH₃ —CH(OH)— Ia-a996—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ia-a997—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ia-a998—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ia-a999—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1000—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1001—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CF₃)—  Ia-a1002—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1003

—CH(OH)—  Ia-a1004

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1005

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1006

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1007

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1008

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1009

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1010

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1011

—CH(OH)—  Ia-a1012

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1013

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1014

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1015

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1016

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1017

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1018

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1019

—CH(OH)—  Ia-a1020

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1021

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1022

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1023

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1024

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1025

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1026

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1027

—CH(OH)—  Ia-a1028

N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1029

N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1030

N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1031

N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1032

N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1033

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1034

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1035

—CH(OH)—  Ia-a1036

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1037

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1038

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1039

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1040

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1041

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1042

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1043

—CH(OH)—  Ia-a1044

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1045

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1046

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1047

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1048

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1049

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1050

—N(C(O)N(H)—(CH₂)₃—OH)—  Ia-a1051

—CH(OH)—  Ia-a1052

—N(C(O)N(H)—CH₂—CH₂—OH)—  Ia-a1053

—N(C(O)N(H)—CH₂—CH₂—F)—  Ia-a1054

—N(C(O)N(H)—CH₂—CH₂—OCH₃)—  Ia-a1055

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1056

—N(C(O)N(H)—CH₂—CH₂—CF₃)—  Ia-a1057

—N(C(O)N(H)—CH₂—CF₃)—  Ia-a1058

—N(C(O)N(H)—(CH₂)₃—OH)—

and pharmaceutically acceptable salts thereof.

5.3 The Indenoisoquinolinone Analogs of Formula (IIa)

The present invention provides Indenoisoquinolinone Analogs according toFormula (Ib), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (Ib).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂ CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(C(CH₃)₃)—.

In one embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In one embodiment, X is —CH(OH)—.

In another embodiment, X is —CH(OH)— and R¹ is —(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —CH(OH)— and R¹ is —(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)_(n)N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R¹)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, m is 2.

In another embodiment, m is 3.

In yet another embodiment, m is 4, 5, or 6.

In a further embodiment, m is 7, 8, or 9.

In yet a further embodiment, m is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is —N(CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₂CH₃)(CH₃),

—NH—CH₂CH₂CH₂CH₃, or

—NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is —N(CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₂CH₃)(CH₃),

—NH—CH₂CH₂CH₂CH₃, or

—NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl;

n is an integer ranging from 1 to 10; and

m is an integer ranging from 2 to 10.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at least one R² is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R 2)(R²); and at leastone R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is —C₃-C₈ monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle, which is substituted with ahydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle, which is substituted with anitrogen-containing 3- to 7-membered monocyclic heterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (Ib) as set forth below:

(Ib)

Compound n —R¹ X Ib-1 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-2 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-3 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-4 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-5 5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-6 6—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ib-7 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ib-8 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ib-9 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)—Ib-10 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ib-11 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₃)— Ib-12 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ib-13 1—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-14 2 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ib-15 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-16 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-17 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ib-18 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-19 1—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-20 2 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ib-21 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-22 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-23 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ib-24 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-25 1—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-26 2 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ib-27 3 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ib-28 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-29 5—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-30 6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ib-31 1 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-322 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-33 3 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ib-34 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-35 5—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-36 6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ib-37 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-38 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-39 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ib-40 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-41 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-42 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ib-43 1 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ib-44 2—(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ib-45 3 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)—Ib-46 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ib-47 5 —(CH₂)_(n)—N(CH₃)₂—N(C(CH₃)₃)— Ib-48 6 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ib-49 1

—N(CH₃)— Ib-50 2

—N(CH₃)— Ib-51 3

—N(CH₃)— Ib-52 4

—N(CH₃)— Ib-53 5

—N(CH₃)— Ib-54 6

—N(CH₃)— Ib-55 1

—N(CH₂CH₃)— Ib-56 2

—N(CH₂CH₃)— Ib-57 3

—N(CH₂CH₃)— Ib-58 4

—N(CH₂CH₃)— Ib-59 5

—N(CH₂CH₃)— Ib-60 6

—N(CH₂CH₃)— Ib-61 1

—N(CH₂CH₂CH₃)— Ib-62 2

—N(CH₂CH₂CH₃)— Ib-63 3

—N(CH₂CH₂CH₃)— Ib-64 4

—N(CH₂CH₂CH₃)— Ib-65 5

—N(CH₂CH₂CH₃)— Ib-66 6

—N(CH₂CH₂CH₃)— Ib-67 1

—N(CH₂CH₂CH₂CH₃)— Ib-68 2

—N(CH₂CH₂CH₂CH₃)— Ib-69 3

—N(CH₂CH₂CH₂CH₃)— Ib-70 4

—N(CH₂CH₂CH₂CH₃)— Ib-71 5

—N(CH₂CH₂CH₂CH₃)— Ib-72 6

—N(CH₂CH₂CH₂CH₃)— Ib-73 1

—N(C(H)(CH₃)(CH₂CH₃))— Ib-74 2

—N(C(H)(CH₃)(CH₂CH₃))— Ib-75 3

—N(C(H)(CH₃)(CH₂CH₃))— Ib-76 4

—N(C(H)(CH₃)(CH₂CH₃))— Ib-77 5

—N(C(H)(CH₃)(CH₂CH₃))— Ib-78 6

—N(C(H)(CH₃)(CH₂CH₃))— Ib-79 1

—N(C(H)(CH₃)₂)— Ib-80 2

—N(C(H)(CH₃)₂)— Ib-81 3

—N(C(H)(CH₃)₂)— Ib-82 4

—N(C(H)(CH₃)₂)— Ib-83 5

—N(C(H)(CH₃)₂)— Ib-84 6

—N(C(H)(CH₃)₂)— Ib-85 1

—N(CH₂C(H)(CH₃)₂)— Ib-86 2

—N(CH₂C(H)(CH₃)₂)— Ib-87 3

—N(CH₂C(H)(CH₃)₂)— Ib-88 4

—N(CH₂C(H)(CH₃)₂)— Ib-89 5

—N(CH₂C(H)(CH₃)₂)— Ib-90 6

—N(CH₂C(H)(CH₃)₂)— Ib-91 1

—N(C(CH₃)₃)— Ib-92 2

—N(C(CH₃)₃)— Ib-93 3

—N(C(CH₃)₃)— Ib-94 4

—N(C(CH₃)₃)— Ib-95 5

—N(C(CH₃)₃)— Ib-96 6

—N(C(CH₃)₃)— Compound m —R¹ X Ib-146 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ib-147 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ib-148 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₃)— Ib-149 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ib-150 6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ib-151 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ib-152 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ib-153 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ib-154 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ib-155 6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ib-156 2 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ib-157 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ib-158 4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-159 5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ib-160 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-161 2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-162 3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ib-163 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-164 5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-165 6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ib-166 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-1673 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-168 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ib-169 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-1706 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-171 2—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-172 3—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-173 4—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-174 5—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-175 6—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-176 2—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-178 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ib-179 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-180 5—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-181 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ib-182 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-183 3—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-184 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ib-185 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)—Ib-186 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-187 2

—N(CH₃)— Ib-188 3

—N(CH₃)— Ib-189 4

—N(CH₃)— Ib-190 5

—N(CH₃)— Ib-191 6

—N(CH₃)— Ib-192 2

—N(CH₃)— Ib-193 3

—N(CH₂CH₃)— Ib-194 4

—N(CH₂CH₃)— Ib-195 5

—N(CH₂CH₃)— Ib-196 6

—N(CH₂CH₃)— Ib-197 2

—N(CH₂CH₃)— Ib-198 3

—N(CH₂CH₃)— Ib-199 4

—N(CH₂CH₂CH₃)— Ib-200 5

—N(CH₂CH₂CH₃)— Ib-201 6

—N(CH₂CH₂CH₃)— Ib-202 2

—N(CH₂CH₂CH₃)— Ib-203 3

—N(CH₂CH₂CH₃)— Ib-204 4

—N(CH₂CH₂CH₃)— Ib-205 5

—N(CH₂CH₂CH₂CH₃)— Ib-206 6

—N(CH₂CH₂CH₂CH₃)— Ib-207 2

—N(CH₂CH₂CH₂CH₃)— Ib-208 3

—N(CH₂CH₂CH₂CH₃)— Ib-209 4

—N(CH₂CH₂CH₂CH₃)— Ib-210 5

—N(CH₂CH₂CH₂CH₃)— Ib-211 6

—N(C(H)(CH₃)(CH₂CH₃))— Ib-212 2

—N(C(H)(CH₃)(CH₂CH₃))— Ib-213 3

—N(C(H)(CH₃)(CH₂CH₃))— Ib-214 4

—N(C(H)(CH₃)(CH₂CH₃))— Ib-215 5

—N(C(H)(CH₃)(CH₂CH₃))— Ib-216 6

—N(C(H)(CH₃)(CH₂CH₃))— Ib-217 2

—N(C(H)(CH₃)₂)— Ib-218 3

—N(C(H)(CH₃)₂)— Ib-219 4

—N(C(H)(CH₃)₂)— Ib-220 5

—N(C(H)(CH₃)₂)— Ib-221 6

—N(C(H)(CH₃)₂)— Ib-222 2

—N(C(H)(CH₃)₂)— Ib-223 3

—N(CH₂C(H)(CH₃)₂)— Ib-224 4

—N(CH₂C(H)(CH₃)₂)— Ib-225 5

—N(CH₂C(H)(CH₃)₂)— Ib-226 6

—N(CH₂C(H)(CH₃)₂)— Compound —R¹ X Ib-267 —CH₂—N(CH₂—CH₃)₂ —N(CH₃)—Ib-268 —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₃)— Ib-269 —CH₂—N(CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ib-270 —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-271—CH₂—N(CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-272 —CH₂—N(CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ib-273 —CH₂—N(CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-274—CH₂—N(CH₂—CH₃)₂ —N(C(CH₃)₃)— Ib-275 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₃)—Ib-276 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₃)— Ib-277 —CH₂—N(CH₂—CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ib-278 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-279—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-280 —CH₂—N(CH₂—CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ib-281 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-282—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(CH₃)₃)— Ib-283 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₃)—Ib-284 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₃)— Ib-285 —CH₂—N(CH₂—CH₂OH)₂—N(CH₂CH₂CH₃)— Ib-286 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₂CH₂CH₃)— Ib-287—CH₂—N(CH₂—CH₂OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-288 —CH₂—N(CH₂—CH₂OH)₂—N(C(H)(CH₃)₂)— Ib-289 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂C(H)(CH₃)₂)— Ib-290—CH₂—N(CH₂—CH₂OH)₂ —N(C(CH₃)₃)— Ib-291 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₃)—Ib-292 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₃)— Ib-293—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ib-294 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(CH₂CH₂CH₂CH₃)— Ib-295 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(C(H)(CH₃)(CH₂CH_(3))—) Ib-296 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(C(H)(CH₃)₂)— Ib-297 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)—Ib-298 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(CH₃)₃)— Ib-299—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(CH₃)— Ib-300 —CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂—N(CH₂CH₃)— Ib-301 —CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ib-302—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(CH₂CH₂CH₂CH₃)— Ib-303—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-304—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(C(H)(CH₃)₂)— Ib-305—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)— Ib-306—CH₂—N(CH₂—CH₂—CH₂N(CH₃)₂)₂ —N(C(CH₃)₃)— Ib-307

—N(CH₃)— Ib-308

—N(CH₂CH₃)— Ib-309

—N(CH₂CH₂CH₃)— Ib-310

—N(CH₂CH₂CH₂CH₃)— Ib-311

—N(C(H)(CH₃)(CH₂CH₃))— Ib-312

—N(C(H)(CH₃)₂)— Ib-313

—N(CH₂C(H)(CH₃)₂)— Ib-314

—N(C(CH₃)₃)— Ib-315

—N(CH₃)— Ib-316

—N(CH₂CH₃)— Ib-317

—N(CH₂CH₂CH₃)— Ib-318

—N(CH₂CH₂CH₂CH₃)— Ib-319

—N(C(H)(CH₃)(CH₂CH₃))— Ib-320

—N(C(H)(CH₃)₂)— Ib-321

—N(CH₂C(H)(CH₃)₂)— Ib-322

—N(C(CH₃)₃)— Ib-323

—N(CH₃)— Ib-324

—N(CH₂CH₃)— Ib-325

—N(CH₂CH₂CH₃)— Ib-326

—N(CH₂CH₂CH₂CH₃)— Ib-327

—N(C(H)(CH₃)(CH₂CH₃))— Ib-328

—N(C(H)(CH₃)₂)— Ib-329

—N(CH₂C(H)(CH₃)₂)— Ib-330

—N(C(CH₃)₃)— Ib-331

—N(CH₃)— Ib-332

—N(CH₂CH₃)— Ib-333

—N(CH₂CH₂CH₃)— Ib-334

—N(CH₂CH₂CH₂CH₃)— Ib-335

—N(C(H)(CH₃)(CH₂CH₃))— Ib-336

—N(C(H)(CH₃)₂)— Ib-337

—N(CH₂C(H)(CH₃)₂)— Ib-338

—N(C(CH₃)₃)— Ib-339

—N(CH₃)— Ib-340

—N(CH₂CH₃)— Ib-341

—N(CH₂CH₂CH₃)— Ib-342

—N(CH₂CH₂CH₂CH₃)— Ib-343

—N(C(H)(CH₃)(CH₂CH₃))— Ib-344

—N(C(H)(CH₃)₂)— Ib-345

—N(CH₂C(H)(CH₃)₂)— Ib-346

—N(C(CH₃)₃)— Ib-347

—N(CH₃)— Ib-348

—N(CH₂CH₃)— Ib-349

—N(CH₂CH₂CH₃)— Ib-350

—N(CH₂CH₂CH₂CH₃)— Ib-351

—N(C(H)(CH₃)(CH₂CH₃))— Ib-352

—N(C(H)(CH₃)₂)— Ib-353

—N(CH₂C(H)(CH₃)₂)— Ib-354

—N(C(CH₃)₃)— Ib-355

—N(CH₃)— Ib-356

—N(CH₂CH₃)— Ib-357

—N(CH₂CH₂CH₃)— Ib-358

—N(CH₂CH₂CH₂CH₃)— Ib-359

—N(C(H)(CH₃)(CH₂CH₃))— Ib-360

—N(C(H)(CH₃)₂)— Ib-361

—N(CH₂C(H)(CH₃)₂)— Ib-362

—N(C(CH₃)₃)— Ib-363

—N(CH₃)— Ib-364

—N(CH₂CH₃)— Ib-365

—N(CH₂CH₂CH₃)— Ib-366

—N(CH₂CH₂CH₂CH₃)— Ib-367

—N(C(H)(CH₃)(CH₂CH₃))— Ib-368

—N(C(H)(CH₃)₂)— Ib-369

—N(CH₂C(H)(CH₃)₂)— Ib-370

—N(C(CH₃)₃)— Ib-371

—N(CH₃)— Ib-372

—N(CH₂CH₃)— Ib-373

—N(CH₂CH₂CH₃)— Ib-374

—N(CH₂CH₂CH₂CH₃)— Ib-375

—N(C(H)(CH₃)(CH₂CH₃))— Ib-376

—N(C(H)(CH₃)₂)— Ib-377

—N(CH₂C(H)(CH₃)₂)— Ib-378

—N(C(CH₃)₃)— Ib-379

—N(CH₃)— Ib-380

—N(CH₂CH₃)— Ib-381

—N(CH₂CH₂CH₃)— Ib-382

—N(CH₂CH₂CH₂CH₃)— Ib-383

—N(C(H)(CH₃)(CH₂CH₃))— Ib-384

—N(C(H)(CH₃)₂)— Ib-385

—N(CH₂C(H)(CH₃)₂)— Ib-386

—N(C(CH₃)₃)— Ib-387

—N(CH₃)— Ib-388

—N(CH₂CH₃)— Ib-389

—N(CH₂CH₂CH₃)— Ib-390

—N(CH₂CH₂CH₂CH₃)— Ib-391

—N(C(H)(CH₃)(CH₂CH₃))— Ib-392

—N(C(H)(CH₃)₂)— Ib-393

—N(CH₂C(H)(CH₃)₂)— Ib-394

—N(C(CH₃)₃)— Ib-395

—N(CH₃)— Ib-396

—N(CH₂CH₃)— Ib-397

—N(CH₂CH₂CH₃)— Ib-398

—N(CH₂CH₂CH₂CH₃)— Ib-399

—N(C(H)(CH₃)(CH₂CH₃))— Ib-400

—N(C(H)(CH₃)₂)— Ib-401

—N(CH₂C(H)(CH₃)₂)— Ib-402

—N(C(CH₃)₃)— Ib-403

—N(CH₃)— Ib-404

—N(CH₂CH₃)— Ib-405

—N(CH₂CH₂CH₃)— Ib-406

—N(CH₂CH₂CH₂CH₃)— Ib-407

—N(C(H)(CH₃)(CH₂CH₃))— Ib-408

—N(C(H)(CH₃)₂)— Ib-409

—N(CH₂C(H)(CH₃)₂)— Ib-410

—N(C(CH₃)₃)— Ib-411

—N(CH₃)— Ib-412

—N(CH₂CH₃)— Ib-413

—N(CH₂CH₂CH₃)— Ib-414

—N(CH₂CH₂CH₂CH₃)— Ib-415

—N(C(H)(CH₃)(CH₂CH₃))— Ib-416

—N(C(H)(CH₃)₂)— Ib-417

—N(CH₂C(H)(CH₃)₂)— Ib-418

—N(C(CH₃)₃)— Ib-419

—N(CH₃)— Ib-420

—N(CH₂CH₃)— Ib-421

—N(CH₂CH₂CH₃)— Ib-422

—N(CH₂CH₂CH₂CH₃)— Ib-423

—N(C(H)(CH₃)(CH₂CH₃))— Ib-424

—N(C(H)(CH₃)₂)— Ib-425

—N(CH₂C(H)(CH₃)₂)— Ib-426

—N(C(CH₃)₃)— Ib-427

—N(CH₃)— Ib-428

—N(CH₂CH₃)— Ib-429

—N(CH₂CH₂CH₃)— Ib-430

—N(CH₂CH₂CH₂CH₃)— Ib-431

—N(C(H)(CH₃)(CH₂CH₃))— Ib-432

—N(C(H)(CH₃)₂)— Ib-433

—N(CH₂C(H)(CH₃)₂)— Ib-434

—N(C(CH₃)₃)— Ib-435

—N(CH₃)— Ib-436

—N(CH₂CH₃)— Ib-437

—N(CH₂CH₂CH₃)— Ib-438

—N(CH₂CH₂CH₂CH₃)— Ib-439

—N(C(H)(CH₃)(CH₂CH₃))— Ib-440

—N(C(H)(CH₃)₂)— Ib-441

—N(CH₂C(H)(CH₃)₂)— Ib-442

—N(C(CH₃)₃)— Ib-443

—N(CH₃)— Ib-444

—N(CH₂CH₃)— Ib-445

—N(CH₂CH₂CH₃)— Ib-446

—N(CH₂CH₂CH₂CH₃)— Ib-447

—N(C(H)(CH₃)(CH₂CH₃))— Ib-448

—N(C(H)(CH₃)₂)— Ib-449

—N(CH₂C(H)(CH₃)₂)— Ib-450

—N(C(CH₃)₃)— Ib-451

—N(CH₃)— Ib-452

—N(CH₂CH₃)— Ib-453

—N(CH₂CH₂CH₃)— Ib-454

—N(CH₂CH₂CH₂CH₃)— Ib-455

—N(C(H)(CH₃)(CH₂CH₃))— Ib-456

—N(C(H)(CH₃)₂)— Ib-457

—N(CH₂C(H)(CH₃)₂)— Ib-458

—N(C(CH₃)₃)— Ib-459

—N(CH₃)— Ib-460

—N(CH₂CH₃)— Ib-461

—N(CH₂CH₂CH₃)— Ib-462

—N(CH₂CH₂CH₂CH₃)— Ib-463

—N(C(H)(CH₃)(CH₂CH₃))— Ib-464

—N(C(H)(CH₃)₂)— Ib-465

—N(CH₂C(H)(CH₃)₂)— Ib-466

—N(C(CH₃)₃)— Ib-467

—N(CH₃)— Ib-468

—N(CH₂CH₃)— Ib-469

—N(CH₂CH₂CH₃)— Ib-470

—N(CH₂CH₂CH₂CH₃)— Ib-471

—N(C(H)(CH₃)(CH₂CH₃))— Ib-472

—N(C(H)(CH₃)₂)— Ib-473

—N(CH₂C(H)(CH₃)₂)— Ib-474

—N(C(CH₃)₃)— Ib-475

—N(CH₃)— Ib-476

—N(CH₂CH₃)— Ib-477

—N(CH₂CH₂CH₃)— Ib-478

—N(CH₂CH₂CH₂CH₃)— Ib-479

—N(C(H)(CH₃)(CH₂CH₃))— Ib-480

—N(C(H)(CH₃)₂)— Ib-481

—N(CH₂C(H)(CH₃)₂)— Ib-482

—N(C(CH₃)₃)— Ib-483

—N(CH₃)— Ib-484

—N(CH₂CH₃)— Ib-485

—N(CH₂CH₂CH₃)— Ib-486

—N(CH₂CH₂CH₂CH₃)— Ib-487

—N(C(H)(CH₃)(CH₂CH₃))— Ib-488

—N(C(H)(CH₃)₂)— Ib-489

—N(CH₂C(H)(CH₃)₂)— Ib-490

—N(C(CH₃)₃)— Ib-491 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₃)— Ib-492—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₃)— Ib-493 —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂CH₂CH₃)— Ib-494 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₂CH₂CH₃)— Ib-495—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-496—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)₂)— Ib-497 —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂C(H)(CH₃)₂)— Ib-498 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(CH₃)₃)— Ib-499—CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₃)— Ib-500 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₃)—Ib-501 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₂CH₃)— Ib-502 —CH₂—CH₂—CH₂—OS(O)₂OH—N(CH₂CH₂CH₂CH₃)— Ib-503 —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(H)(CH₃)(CH₂CH₃))—Ib-504 —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(H)(CH₃)₂)— Ib-505—CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂C(H)(CH₃)₂)— Ib-506 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(CH₃)₃)— Ib-507

—N(CH₃)— Ib-508

—N(CH₂CH₃)— Ib-509

—N(CH₂CH₂CH₃)— Ib-510

—N(CH₂CH₂CH₂CH₃)— Ib-511

—N(C(H)(CH₃)(CH₂CH₃))— Ib-512

—N(C(H)(CH₃)₂)— Ib-513

—N(CH₂C(H)(CH₃)₂)— Ib-514

—N(C(CH₃)₃)— Ib-515

—N(CH₃)— Ib-516

—N(CH₂CH₃)— Ib-517

—N(CH₂CH₂CH₃)— Ib-518

—N(CH₂CH₂CH₂CH₃)— Ib-519

—N(C(H)(CH₃)(CH₂CH₃))— Ib-520

—N(C(H)(CH₃)₂)— Ib-521

—N(CH₂C(H)(CH₃)₂)— Ib-522

—N(C(CH₃)₃)— Ib-523 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₃)— Ib-524—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ib-525 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂—N(CH₂CH₂CH₃)— Ib-526 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₂CH₃)—Ib-527 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-528—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ib-529—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-530—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(CH₃)₃)— Ib-531 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₃)— Ib-532 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ib-533—CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₃)— Ib-534 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ib-535 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ib-536 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ib-537—CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-538 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(CH₃)₃)— Ib-539

—N(CH₃)— Ib-540

—N(CH₂CH₃)— Ib-541

—N(CH₂CH₂CH₃)— Ib-542

—N(CH₂CH₂CH₂CH₃)— Ib-543

—N(C(H)(CH₃)(CH₂CH₃))— Ib-544

—N(C(H)(CH₃)₂)— Ib-545

—N(CH₂C(H)(CH₃)₂)— Ib-546

—N(C(CH₃)₃)— Ib-547

—N(CH₃)— Ib-548

—N(CH₂CH₃)— Ib-549

—N(CH₂CH₂CH₃)— Ib-550

—N(CH₂CH₂CH₂CH₃)— Ib-551

—N(C(H)(CH₃)(CH₂CH₃))— Ib-552

—N(C(H)(CH₃)₂)— Ib-553

—N(CH₂C(H)(CH₃)₂)— Ib-554

—N(C(CH₃)₃)— Ib-555

—N(CH₃)— Ib-556

—N(CH₂CH₃)— Ib-557

—N(CH₂CH₂CH₃)— Ib-558

—N(CH₂CH₂CH₂CH₃)— Ib-559

—N(C(H)(CH₃)(CH₂CH₃))— Ib-560

—N(C(H)(CH₃)₂)— Ib-561

—N(CH₂C(H)(CH₃)₂)— Ib-562

—N(C(CH₃)₃)— Ib-563

—N(CH₃)— Ib-564

—N(CH₂CH₃)— Ib-565

—N(CH₂CH₂CH₃)— Ib-566

—N(CH₂CH₂CH₂CH₃)— Ib-567

—N(C(H)(CH₃)(CH₂CH₃))— Ib-568

—N(C(H)(CH₃)₂)— Ib-569

—N(CH₂C(H)(CH₃)₂)— Ib-570

—N(C(CH₃)₃)— Ib-571

—N(CH₃)— Ib-572

—N(CH₂CH₃)— Ib-573

—N(CH₂CH₂CH₃)— Ib-574

—N(CH₂CH₂CH₂CH₃)— Ib-575

—N(C(H)(CH₃)(CH₂CH₃))— Ib-576

—N(C(H)(CH₃)₂)— Ib-577

—N(CH₂C(H)(CH₃)₂)— Ib-578

—N(C(CH₃)₃)— Ib-579

—N(CH₃)— Ib-580

—N(CH₂CH₃)— Ib-581

—N(CH₂CH₂CH₃)— Ib-582

—N(CH₂CH₂CH₂CH₃)— Ib-583

—N(C(H)(CH₃)(CH₂CH₃))— Ib-584

—N(C(H)(CH₃)₂)— Ib-585

—N(CH₂C(H)(CH₃)₂)— Ib-586

—N(C(CH₃)₃)— Ib-587

—N(CH₃)— Ib-588

—N(CH₂CH₃)— Ib-589

—N(CH₂CH₂CH₃)— Ib-590

—N(CH₂CH₂CH₂CH₃)— Ib-591

—N(C(H)(CH₃)(CH₂CH₃))— Ib-592

—N(C(H)(CH₃)₂)— Ib-593

—N(CH₂C(H)(CH₃)₂)— Ib-594

—N(C(CH₃)₃)— Ib-595

—N(CH₃)— Ib-596

—N(CH₂CH₃)— Ib-597

—N(CH₂CH₂CH₃)— Ib-598

—N(CH₂CH₂CH₂CH₃)— Ib-599

—N(C(H)(CH₃)(CH₂CH₃))— Ib-600

—N(C(H)(CH₃)₂)— Ib-601

—N(CH₂C(H)(CH₃)₂)— Ib-602

—N(C(CH₃)₃)— Ib-603

—N(CH₃)— Ib-604

—N(CH₂CH₃)— Ib-605

—N(CH₂CH₂CH₃)— Ib-606

—N(CH₂CH₂CH₂CH₃)— Ib-607

—N(C(H)(CH₃)(CH₂CH₃))— Ib-608

—N(C(H)(CH₃)₂)— Ib-609

—N(CH₂C(H)(CH₃)₂)— Ib-610

—N(C(CH₃)₃)— Ib-611 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₃)— Ib-612—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₃)— Ib-613—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ib-614—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ib-615—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ib-616—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ib-617—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ib-618—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(CH₃)₃)— Ib-619

—N(CH₃)— Ib-620

—N(CH₂CH₃)— Ib-621

—N(CH₂CH₂CH₃)— Ib-622

—N(CH₂CH₂CH₂CH₃)— Ib-623

—N(C(H)(CH₃)(CH₂CH₃))— Ib-624

—N(C(H)(CH₃)₂)— Ib-625

—N(CH₂C(H)(CH₃)₂)— Ib-626

—N(C(CH₃)₃)— Ib-627

—N(CH₃)— Ib-628

—N(CH₂CH₃)— Ib-629

—N(CH₂CH₂CH₃)— Ib-630

—N(CH₂CH₂CH₂CH₃)— Ib-631

—N(C(H)(CH₃)(CH₂CH₃))— Ib-632

—N(C(H)(CH₃)₂)— Ib-633

—N(CH₂C(H)(CH₃)₂)— Ib-634

—N(C(CH₃)₃)— Ib-635

—N(CH₃)— Ib-636

—N(CH₂CH₃)— Ib-637

—N(CH₂CH₂CH₃)— Ib-638

—N(CH₂CH₂CH₂CH₃)— Ib-639

—N(C(H)(CH₃)(CH₂CH₃))— Ib-640

—N(C(H)(CH₃)₂)— Ib-641

—N(CH₂C(H)(CH₃)₂)— Ib-642

—N(C(CH₃)₃)— Ib-643

—N(CH₃)— Ib-644

—N(CH₂CH₃)— Ib-645

—N(CH₂CH₂CH₃)— Ib-646

—N(CH₂CH₂CH₂CH₃)— Ib-647

—N(C(H)(CH₃)(CH₂CH₃))— Ib-648

—N(C(H)(CH₃)₂)— Ib-649

—N(CH₂C(H)(CH₃)₂)— Ib-650

—N(C(CH₃)₃)— Ib-651

—N(CH₃)— Ib-652

—N(CH₂CH₃)— Ib-653

—N(CH₂CH₂CH₃)— Ib-654

—N(CH₂CH₂CH₂CH₃)— Ib-655

—N(C(H)(CH₃)(CH₂CH₃))— Ib-656

—N(C(H)(CH₃)₂)— Ib-657

—N(CH₂C(H)(CH₃)₂)— Ib-658

—N(C(CH₃)₃)— Ib-659

—N(CH₃)— Ib-660

—N(CH₂CH₃)— Ib-661

—N(CH₂CH₂CH₃)— Ib-662

—N(CH₂CH₂CH₂CH₃)— Ib-663

—N(C(H)(CH₃)(CH₂CH₃))— Ib-664

—N(C(H)(CH₃)₂)— Ib-665

—N(CH₂C(H)(CH₃)₂)— Ib-666

—N(C(CH₃)₃)— Ib-667

—N(CH₃)— Ib-668

—N(CH₂CH₃)— Ib-669

—N(CH₂CH₂CH₃)— Ib-670

—N(CH₂CH₂CH₂CH₃)— Ib-671

—N(C(H)(CH₃)(CH₂CH₃))— Ib-672

—N(C(H)(CH₃)₂)— Ib-673

—N(CH₂C(H)(CH₃)₂)— Ib-674

—N(C(CH₃)₃)— Ib-675

—N(CH₃)— Ib-676

—N(CH₂CH₃)— Ib-677

—N(CH₂CH₂CH₃)— Ib-678

—N(CH₂CH₂CH₂CH₃)— Ib-679

—N(C(H)(CH₃)(CH₂CH₃))— Ib-680

—N(C(H)(CH₃)₂)— Ib-681

—N(CH₂C(H)(CH₃)₂)— Ib-682

—N(C(CH₃)₃)— Ib-683

—N(CH₃)— Ib-684

—N(CH₂CH₃)— Ib-685

—N(CH₂CH₂CH₃)— Ib-686

—N(CH₂CH₂CH₂CH₃)— Ib-687

—N(C(H)(CH₃)(CH₂CH₃))— Ib-688

—N(C(H)(CH₃)₂)— Ib-689

—N(CH₂C(H)(CH₃)₂)— Ib-690

—N(C(CH₃)₃)— Ib-691

—N(CH₃)— Ib-692

—N(CH₂CH₃)— Ib-693

—N(CH₂CH₂CH₃)— Ib-694

—N(CH₂CH₂CH₂CH₃)— Ib-695

—N(C(H)(CH₃)(CH₂CH₃))— Ib-696

—N(C(H)(CH₃)₂)— Ib-697

—N(CH₂C(H)(CH₃)₂)— Ib-698

—N(C(CH₃)₃)— Ib-699

—N(CH₃)— Ib-700

—N(CH₂CH₃)— Ib-701

—N(CH₂CH₂CH₃)— Ib-702

—N(CH₂CH₂CH₂CH₃)— Ib-703

—N(C(H)(CH₃)(CH₂CH₃))— Ib-704

—N(C(H)(CH₃)₂)— Ib-705

—N(CH₂C(H)(CH₃)₂)— Ib-706

—N(C(CH₃)₃)— Ib-707

—N(CH₃)— Ib-708

—N(CH₂CH₃)— Ib-709

—N(CH₂CH₂CH₃)— Ib-710

—N(CH₂CH₂CH₂CH₃)— Ib-711

—N(C(H)(CH₃)(CH₂CH₃))— Ib-712

—N(C(H)(CH₃)₂)— Ib-713

—N(CH₂C(H)(CH₃)₂)— Ib-714

—N(C(CH₃)₃)— Ib-715

—N(CH₃)— Ib-716

—N(CH₂CH₃)— Ib-717

—N(CH₂CH₂CH₃)— Ib-718

—N(CH₂CH₂CH₂CH₃)— Ib-719

—N(C(H)(CH₃)(CH₂CH₃))— Ib-720

—N(C(H)(CH₃)₂)— Ib-721

—N(CH₂C(H)(CH₃)₂)— Ib-722

—N(C(CH₃)₃)— Ib-723

—N(CH₃)— Ib-724

—N(CH₂CH₃)— Ib-725

—N(CH₂CH₂CH₃)— Ib-726

—N(CH₂CH₂CH₂CH₃)— Ib-727

—N(C(H)(CH₃)(CH₂CH₃))— Ib-728

—N(C(H)(CH₃)₂)— Ib-729

—N(CH₂C(H)(CH₃)₂)— Ib-730

—N(C(CH₃)₃)— Ib-731

—N(CH₃)— Ib-732

—N(CH₂CH₃)— Ib-733

—N(CH₂CH₂CH₃)— Ib-734

—N(CH₂CH₂CH₂CH₃)— Ib-735

—N(C(H)(CH₃)(CH₂CH₃))— Ib-736

—N(C(H)(CH₃)₂)— Ib-737

—N(CH₂C(H)(CH₃)₂)— Ib-738

—N(C(CH₃)₃)— Ib-739

—N(CH₃)— Ib-740

—N(CH₂CH₃)— Ib-741

—N(CH₂CH₂CH₃)— Ib-742

—N(CH₂CH₂CH₂CH₃)— Ib-743

—N(C(H)(CH₃)(CH₂CH₃))— Ib-744

—N(C(H)(CH₃)₂)— Ib-745

—N(CH₂C(H)(CH₃)₂)— Ib-746

—N(C(CH₃)₃)— Ib-747

—N(CH₃)— Ib-748

—N(CH₂CH₃)— Ib-749

—N(CH₂CH₂CH₃)— Ib-750

—N(CH₂CH₂CH₂CH₃)— Ib-751

—N(C(H)(CH₃)(CH₂CH₃))— Ib-752

—N(C(H)(CH₃)₂)— Ib-753

—N(CH₂C(H)(CH₃)₂)— Ib-754

—N(C(CH₃)₃)— Ib-755

—N(CH₃)— Ib-756

—N(CH₂CH₃)— Ib-757

—N(CH₂CH₂CH₃)— Ib-758

—N(CH₂CH₂CH₂CH₃)— Ib-759

—N(C(H)(CH₃)(CH₂CH₃))— Ib-760

—N(C(H)(CH₃)₂)— Ib-761

—N(CH₂C(H)(CH₃)₂)— Ib-762

—N(C(CH₃)₃)— Ib-763

—N(CH₃)— Ib-764

—N(CH₂CH₃)— Ib-765

—N(CH₂CH₂CH₃)— Ib-766

—N(CH₂CH₂CH₂CH₃)— Ib-767

—N(C(H)(CH₃)(CH₂CH₃))— Ib-768

—N(C(H)(CH₃)₂)— Ib-769

—N(CH₂C(H)(CH₃)₂)— Ib-770

—N(C(CH₃)₃)— Ib-771

—N(CH₃)— Ib-772

—N(CH₂CH₃)— Ib-773

—N(CH₂CH₂CH₃)— Ib-774

—N(CH₂CH₂CH₂CH₃)— Ib-775

—N(C(H)(CH₃)(CH₂CH₃))— Ib-776

—N(C(H)(CH₃)₂)— Ib-777

—N(CH₂C(H)(CH₃)₂)— Ib-778

—N(C(CH₃)₃)— Ib-779 —CH₂—NH—CH₃ —N(CH₃)— Ib-780 —CH₂—NH—CH₃ —N(CH₂CH₃)—Ib-781 —CH₂—NH—CH₃ —N(CH₂CH₂CH₃)— Ib-782 —CH₂—NH—CH₃ —N(CH₂CH₂CH₂CH₃)—Ib-783 —CH₂—NH—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ib-784 —CH₂—NH—CH₃—N(C(H)(CH₃)₂)— Ib-785 —CH₂—NH—CH₃ —N(CH₂C(H)(CH₃)₂)— Ib-786 —CH₂—NH—CH₃—N(C(CH₃)₃)— Ib-787 —CH₂—NH—CH₂—CH₃ —N(CH₃)— Ib-788 —CH₂—NH—CH₂—CH₃—N(CH₂CH₃)— Ib-789 —CH₂—NH—CH₂—CH₃ —N(CH₂CH₂CH₃)— Ib-790 —CH₂—NH—CH₂—CH₃—N(CH₂CH₂CH₂CH₃)— Ib-791 —CH₂—NH—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ib-792—CH₂—NH—CH₂—CH₃ —N(C(H)(CH₃)₂)— Ib-793 —CH₂—NH—CH₂—CH₃—N(CH₂C(H)(CH₃)₂)— Ib-794 —CH₂—NH—CH₂—CH₃ —N(C(CH₃)₃)— Ib-795—CH₂—NH—CH₂—CH₂—CH₃ —N(CH₃)— Ib-796 —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₃)—Ib-797 —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₂CH₃)— Ib-798 —CH₂—NH—CH₂—CH₂—CH₃—N(CH₂CH₂CH₂CH₃)— Ib-799 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ib-800 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(H)(CH₃)₂)— Ib-801 —CH₂—NH—CH₂—CH₂—CH₃—N(CH₂C(H)(CH₃)₂)— Ib-802 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(CH₃)₃)— Ib-803

—N(CH₃)— Ib-804

—N(CH₂CH₃)— Ib-805

—N(CH₂CH₂CH₃)— Ib-806

—N(CH₂CH₂CH₂CH₃)— Ib-807

—N(C(H)(CH₃)(CH₂CH₃))— Ib-808

—N(C(H)(CH₃)₂)— Ib-809

—N(CH₂C(H)(CH₃)₂)— Ib-810

—N(C(CH₃)₃)— Ib-811

—N(CH₃)— Ib-812

—N(CH₂CH₃)— Ib-813

—N(CH₂CH₂CH₃)— Ib-814

—N(CH₂CH₂CH₂CH₃)— Ib-815

—N(C(H)(CH₃)(CH₂CH₃))— Ib-816

—N(C(H)(CH₃)₂)— Ib-817

—N(CH₂C(H)(CH₃)₂)— Ib-818

—N(C(CH₃)₃)— Ib-819

—N(CH₃)— Ib-820

—N(CH₂CH₃)— Ib-821

—N(CH₂CH₂CH₃)— Ib-822

—N(CH₂CH₂CH₂CH₃)— Ib-823

—N(C(H)(CH₃)(CH₂CH₃))— Ib-824

—N(C(H)(CH₃)₂)— Ib-825

—N(CH₂C(H)(CH₃)₂)— Ib-826

—N(C(CH₃)₃)— Ib-827

—N(CH₃)— Ib-828

—N(CH₂CH₃)— Ib-829

—N(CH₂CH₂CH₃)— Ib-830

—N(CH₂CH₂CH₂CH₃)— Ib-831

—N(C(H)(CH₃)(CH₂CH₃))— Ib-832

—N(C(H)(CH₃)₂)— Ib-833

—N(CH₂C(H)(CH₃)₂)— Ib-834

—N(C(CH₃)₃)— Ib-835

—N(CH₃)— Ib-836

—N(CH₂CH₃)— Ib-837

—N(CH₂CH₂CH₃)— Ib-838

—N(CH₂CH₂CH₂CH₃)— Ib-839

—N(C(H)(CH₃)(CH₂CH₃))— Ib-840

—N(C(H)(CH₃)₂)— Ib-841

—N(CH₂C(H)(CH₃)₂)— Ib-842

—N(C(CH₃)₃)— Ib-843

—N(CH₃)— Ib-844

—N(CH₂CH₃)— Ib-845

—N(CH₂CH₂CH₃)— Ib-846

—N(CH₂CH₂CH₂CH₃)— Ib-847

—N(C(H)(CH₃)(CH₂CH₃))— Ib-848

—N(C(H)(CH₃)₂)— Ib-849

—N(CH₂C(H)(CH₃)₂)— Ib-850

—N(C(CH₃)₃)— Ib-851

—N(CH₃)— Ib-852

—N(CH₂CH₃)— Ib-853

—N(CH₂CH₂CH₃)— Ib-854

—N(CH₂CH₂CH₂CH₃)— Ib-855

—N(C(H)(CH₃)(CH₂CH₃))— Ib-856

—N(C(H)(CH₃)₂)— Ib-857

—N(CH₂C(H)(CH₃)₂)— Ib-858

—N(C(CH₃)₃)— Ib-859

—N(CH₃)— Ib-860

—N(CH₂CH₃)— Ib-861

—N(CH₂CH₂CH₃)— Ib-862

—N(CH₂CH₂CH₂CH₃)— Ib-863

—N(C(H)(CH₃)(CH₂CH₃))— Ib-864

—N(C(H)(CH₃)₂)— Ib-865

—N(CH₂C(H)(CH₃)₂)— Ib-866

—N(C(CH₃)₃)— Ib-867

—N(CH₃)— Ib-868

—N(CH₂CH₃)— Ib-869

—N(CH₂CH₂CH₃)— Ib-870

—N(CH₂CH₂CH₂CH₃)— Ib-871

—N(C(H)(CH₃)(CH₂CH₃))— Ib-872

—N(C(H)(CH₃)₂)— Ib-873

—N(CH₂C(H)(CH₃)₂)— Ib-874

—N(C(CH₃)₃)— Ib-875

—N(CH₃)— Ib-876

—N(CH₂CH₃)— Ib-877

—N(CH₂CH₂CH₃)— Ib-878

—N(CH₂CH₂CH₂CH₃)— Ib-879

—N(C(H)(CH₃)(CH₂CH₃))— Ib-880

—N(C(H)(CH₃)₂)— Ib-881

—N(CH₂C(H)(CH₃)₂)— Ib-882

—N(C(CH₃)₃)— Ib-883

—N(CH₃)— Ib-884

—N(CH₂CH₃)— Ib-885

—N(CH₂CH₂CH₃)— Ib-886

—N(CH₂CH₂CH₂CH₃)— Ib-887

—N(C(H)(CH₃)(CH₂CH₃))— Ib-888

—N(C(H)(CH₃)₂)— Ib-889

—N(CH₂C(H)(CH₃)₂)— Ib-890

—N(C(CH₃)₃)— Ib-891

—N(CH₃)— Ib-892

—N(CH₂CH₃)— Ib-893

—N(CH₂CH₂CH₃)— Ib-894

—N(CH₂CH₂CH₂CH₃)— Ib-895

—N(C(H)(CH₃)(CH₂CH₃))— Ib-896

—N(C(H)(CH₃)₂)— Ib-897

—N(CH₂C(H)(CH₃)₂)— Ib-898

—N(C(CH₃)₃)— Ib-899

—N(CH₃)— Ib-900

—N(CH₂CH₃)— Ib-901

—N(CH₂CH₂CH₃)— Ib-902

—N(CH₂CH₂CH₂CH₃)— Ib-903

—N(C(H)(CH₃)(CH₂CH₃))— Ib-904

—N(C(H)(CH₃)₂)— Ib-905

—N(CH₂C(H)(CH₃)₂)— Ib-906

—N(C(CH₃)₃)— Ib-907

—N(CH₃)— Ib-908

—N(CH₂CH₃)— Ib-909

—N(CH₂CH₂CH₃)— Ib-910

—N(CH₂CH₂CH₂CH₃)— Ib-911

—N(C(H)(CH₃)(CH₂CH₃))— Ib-912

—N(C(H)(CH₃)₂)— Ib-913

—N(CH₂C(H)(CH₃)₂)— Ib-914

—N(C(CH₃)₃)— Ib-915

—N(CH₃)— Ib-916

—N(CH₂CH₃)— Ib-917

—N(CH₂CH₂CH₃)— Ib-918

—N(CH₂CH₂CH₂CH₃)— Ib-919

—N(C(H)(CH₃)(CH₂CH₃))— Ib-920

—N(C(H)(CH₃)₂)— Ib-921

—N(CH₂C(H)(CH₃)₂)— Ib-922

—N(C(CH₃)₃)— Ib-923

—N(CH₃)— Ib-924

—N(CH₂CH₃)— Ib-925

—N(CH₂CH₂CH₃)— Ib-926

—N(CH₂CH₂CH₂CH₃)— Ib-927

—N(C(H)(CH₃)(CH₂CH₃))— Ib-928

—N(C(H)(CH₃)₂)— Ib-929

—N(CH₂C(H)(CH₃)₂)— Ib-930

—N(C(CH₃)₃)— Ib-931

—N(CH₃)— Ib-932

—N(CH₂CH₃)— Ib-933

—N(CH₂CH₂CH₃)— Ib-934

—N(CH₂CH₂CH₂CH₃)— Ib-935

—N(C(H)(CH₃)(CH₂CH₃))— Ib-936

—N(C(H)(CH₃)₂)— Ib-937

—N(CH₂C(H)(CH₃)₂)— Ib-938

—N(C(CH₃)₃)— Ib-939

—N(CH₃)— Ib-940

—N(CH₂CH₃)— Ib-941

—N(CH₂CH₂CH₃)— Ib-942

—N(CH₂CH₂CH₂CH₃)— Ib-943

—N(C(H)(CH₃)(CH₂CH₃))— Ib-944

—N(C(H)(CH₃)₂)— Ib-945

—N(CH₂C(H)(CH₃)₂)— Ib-946

—N(C(CH₃)₃)— Ib-947

—N(CH₃)— Ib-948

—N(CH₂CH₃)— Ib-949

—N(CH₂CH₂CH₃)— Ib-950

—N(CH₂CH₂CH₂CH₃)— Ib-951

—N(C(H)(CH₃)(CH₂CH₃))— Ib-952

—N(C(H)(CH₃)₂)— Ib-953

—N(CH₂C(H)(CH₃)₂)— Ib-954

—N(C(CH₃)₃)— Ib-955

—N(CH₃)— Ib-956

—N(CH₂CH₃)— Ib-957

—N(CH₂CH₂CH₃)— Ib-958

—N(CH₂CH₂CH₂CH₃)— Ib-959

—N(C(H)(CH₃)(CH₂CH₃))— Ib-960

—N(C(H)(CH₃)₂)— Ib-961

—N(CH₂C(H)(CH₃)₂)— Ib-962

—N(C(CH₃)₃)— Ib-963 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₃)— Ib-964—CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ib-965 —CH₂—N(CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ib-966 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ib-967—CH₂—N(CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ib-968 —CH₂—N(CH₂CH₃)(CH₃)—N(C(H)(CH₃)₂)— Ib-969 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ib-970—CH₂—N(CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ib-971 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₃)—Ib-972 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ib-973 —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ib-974 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ib-975—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ib-976—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ib-977 —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(CH₂C(H)(CH₃)₂)— Ib-978 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ib-979—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₃)— Ib-980 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(CH₂CH₃)— Ib-981 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₃)— Ib-982—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ib-983—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ib-984—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ib-985—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ib-986—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ib-987 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₃)— Ib-988 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₃)— Ib-989—CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₂CH₃)— Ib-990 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₂CH₂CH₂CH₃)— Ib-991 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ib-992 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)₂)— Ib-993 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₂C(H)(CH₃)₂)— Ib-994 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(CH₃)₃)— Ib-995—CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₃)— Ib-996 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₃)—Ib-997 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₂CH₃)— Ib-998 —CH₂—NH—CH₂CH₂—O—CH₃—N(CH₂CH₂CH₂CH₃)— Ib-999 —CH₂—NH—CH₂CH₂—O—CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ib-1000 —CH₂—NH—CH₂CH₂—O—CH₃ —N(C(H)(CH₃)₂)— Ib-1001—CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂C(H)(CH₃)₂)— Ib-1002 —CH₂—NH—CH₂CH₂—O—CH₃—N(C(CH₃)₃)— Ib-1003

—N(CH₃)— Ib-1004

—N(CH₂CH₃)— Ib-1005

—N(CH₂CH₂CH₃)— Ib-1006

—N(CH₂CH₂CH₂CH₃)— Ib-1007

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1008

—N(C(H)(CH₃)₂)— Ib-1009

—N(CH₂C(H)(CH₃)₂)— Ib-1010

—N(C(CH₃)₃)— Ib-1011

—N(CH₃)— Ib-1012

—N(CH₂CH₃)— Ib-1013

—N(CH₂CH₂CH₃)— Ib-1014

—N(CH₂CH₂CH₂CH₃)— Ib-1015

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1016

—N(C(H)(CH₃)₂)— Ib-1017

—N(CH₂C(H)(CH₃)₂)— Ib-1018

—N(C(CH₃)₃)— Ib-1019

—N(CH₃)— Ib-1020

—N(CH₂CH₃)— Ib-1021

—N(CH₂CH₂CH₃)— Ib-1022

—N(CH₂CH₂CH₂CH₃)— Ib-1023

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1024

—N(C(H)(CH₃)₂)— Ib-1025

—N(CH₂C(H)(CH₃)₂)— Ib-1026

—N(C(CH₃)₃)— Ib-1027

—N(CH₃)— Ib-1028

—N(CH₂CH₃)— Ib-1029

—N(CH₂CH₂CH₃)— Ib-1030

—N(CH₂CH₂CH₂CH₃)— Ib-1031

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1032

—N(C(H)(CH₃)₂)— Ib-1033

—N(CH₂C(H)(CH₃)₂)— Ib-1034

—N(C(CH₃)₃)— Ib-1035

—N(CH₃)— Ib-1036

—N(CH₂CH₃)— Ib-1037

—N(CH₂CH₂CH₃)— Ib-1038

—N(CH₂CH₂CH₂CH₃)— Ib-1039

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1040

—N(C(H)(CH₃)₂)— Ib-1041

—N(CH₂C(H)(CH₃)₂)— Ib-1042

—N(C(CH₃)₃)— Ib-1043

—N(CH₃)— Ib-1044

—N(CH₂CH₃)— Ib-1045

—N(CH₂CH₂CH₃)— Ib-1046

—N(CH₂CH₂CH₂CH₃)— Ib-1047

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1048

—N(C(H)(CH₃)₂)— Ib-1049

—N(CH₂C(H)(CH₃)₂)— Ib-1050

—N(C(CH₃)₃)— Ib-1051

—N(CH₃)— Ib-1052

—N(CH₂CH₃)— Ib-1053

—N(CH₂CH₂CH₃)— Ib-1054

—N(CH₂CH₂CH₂CH₃)— Ib-1055

—N(C(H)(CH₃)(CH₂CH₃))— Ib-1056

—N(C(H)(CH₃)₂)— Ib-1057

—N(CH₂C(H)(CH₃)₂)— Ib-1058

—N(C(CH₃)₃)— Compound n —R¹ X Ib-b1 1 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b22 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b3 3 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b44 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b5 5 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b66 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ib-b7 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b8 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b9 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b10 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b11 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b12 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b13 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b14 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b15 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b16 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b17 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b18 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b19 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b20 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b21 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b22 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b23 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b24 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b25 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b26 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b27 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b28 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b29 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b30 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b31 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ib-b32 2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b33 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ib-b34 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b35 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b36 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ib-b37 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b38 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b39 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ib-b40 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b41 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b42 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ib-b43 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b44 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b45 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ib-b46 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b47 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b48 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ib-b49 1

—CH(OH)— Ib-b50 2

—CH(OH)— Ib-b51 3

—CH(OH)— Ib-b52 4

—CH(OH)— Ib-b53 5

—CH(OH)— Ib-b54 6

—CH(OH)— Ib-b55 1

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b56 2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b57 3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b58 4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b59 5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b60 6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b61 1

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b62 2

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b63 3

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b64 4

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b65 5

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b66 6

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b67 1

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b68 2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b69 3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b70 4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b71 5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b72 6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b73 1

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b74 2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b75 3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b76 4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b77 5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b78 6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b79 1

—N(CH₂—CH₂—OH)— Ib-b80 2

—N(CH₂—CH₂—OH)— Ib-b81 3

—N(CH₂—CH₂—OH)— Ib-b82 4

—N(CH₂—CH₂—OH)— Ib-b83 5

—N(CH₂—CH₂—OH)— Ib-b84 6

—N(CH₂—CH₂—OH)— Ib-b85 1

—N(CH₂—CH₂—F)— Ib-b86 2

—N(CH₂—CH₂—F)— Ib-b87 3

—N(CH₂—CH₂—F)— Ib-b88 4

—N(CH₂—CH₂—F)— Ib-b89 5

—N(CH₂—CH₂—F)— Ib-b90 6

—N(CH₂—CH₂—F)— Ib-b91 1

—N(CH₂—CH₂—OCH₃)— Ib-b92 2

—N(CH₂—CH₂—OCH₃)— Ib-b93 3

—N(CH₂—CH₂—OCH₃)— Ib-b94 4

—N(CH₂—CH₂—OCH₃)— Ib-b95 5

—N(CH₂—CH₂—OCH₃)— Ib-b96 6

—N(CH₂—CH₂—OCH₃)— Compound m —R¹ X Ib-b146 2 —O—(CH₂)_(m)—N(CH₃)₂—CH(OH)— Ib-b147 3 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ib-b148 4—O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ib-b149 5 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)—Ib-b150 6 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ib-b151 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b152 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b153 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b154 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b155 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b156 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b157 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b158 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b159 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b160 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b161 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b162 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b163 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b164 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b165 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b166 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b167 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b168 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b169 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b170 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b171 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ib-b172 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b173 4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b174 5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ib-b175 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ib-b176 2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b178 3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ib-b179 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b180 5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ib-b181 6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ib-b182 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b1833 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b184 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ib-b185 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)—Ib-b186 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ib-b187 2

—CH(OH)— Ib-b188 3

—CH(OH)— Ib-b189 4

—CH(OH)— Ib-b190 5

—CH(OH)— Ib-b191 6

—CH(OH)— Ib-b192 2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b193 3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b194 4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b195 5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b196 6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b197 2

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b198 3

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b199 4

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b200 5

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b201 6

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b202 2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b203 3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b204 4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b205 5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b206 6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b207 2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b208 3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b209 4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b210 5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b211 6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b212 2

—N(CH₂—CH₂—OH)— Ib-b213 3

—N(CH₂—CH₂—OH)— Ib-b214 4

—N(CH₂—CH₂—OH)— Ib-b215 5

—N(CH₂—CH₂—OH)— Ib-b216 6

—N(CH₂—CH₂—OH)— Ib-b217 2

—N(CH₂—CH₂—F)— Ib-b218 3

—N(CH₂—CH₂—F)— Ib-b219 4

—N(CH₂—CH₂—F)— Ib-b220 5

—N(CH₂—CH₂—F)— Ib-b221 6

—N(CH₂—CH₂—F)— Ib-b222 2

—N(CH₂—CH₂—OCH₃)— Ib-b223 3

—N(CH₂—CH₂—OCH₃)— Ib-b224 4

—N(CH₂—CH₂—OCH₃)— Ib-b225 5

—N(CH₂—CH₂—OCH₃)— Ib-b226 6

—N(CH₂—CH₂—OCH₃)— Compound —R¹ X Ib-b267 —CH₂—N(CH₂—CH₃)₂ —CH(OH)—Ib-b268 —CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b269—CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b270 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b271 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b275 —CH₂—N(CH₂—CH₂—CH₃)₂ —CH(OH)— Ib-b276—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b277—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b278—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b279—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b283—CH₂—N(CH₂—CH₂OH)₂ —CH(OH)— Ib-b284 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b285 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b286 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b291 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)—Ib-b292 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b293—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b294—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b295—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b296—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b297—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ib-b298—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b299—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)— Ib-b300—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b301—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b302—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b303—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b304—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b305—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ib-b306—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ N(C(O)N(H)—(CH₂)₃—OH)— Ib-b307

—CH(OH)— Ib-b308

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b309

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b310

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b311

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b312

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b313

—N(C(O)N(H)—CH₂—CF₃)— Ib-b314

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b315

—CH(OH)— Ib-b316

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b317

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b318

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b319

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b320

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b321

—N(C(O)N(H)—CH₂—CF₃)— Ib-b322

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b323

—CH(OH)— Ib-b324

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b325

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b326

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b327

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b328

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b329

—N(C(O)N(H)—CH₂—CF₃)— Ib-b330

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b331

—CH(OH)— Ib-b332

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b333

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b334

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b335

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b336

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b337

—N(C(O)N(H)—CH₂—CF₃)— Ib-b338

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b339

—CH(OH)— Ib-b340

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b341

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b342

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b343

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b344

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b345

—N(C(O)N(H)—CH₂—CF₃)— Ib-b346

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b347

—CH(OH)— Ib-b348

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b349

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b350

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b351

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b352

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b353

—N(C(O)N(H)—CH₂—CF₃)— Ib-b354

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b355

—CH(OH)— Ib-b356

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b357

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b358

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b359

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b360

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b361

—N(C(O)N(H)—CH₂—CF₃)— Ib-b362

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b363

—CH(OH)— Ib-b364

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b365

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b366

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b367

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b368

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b369

—N(C(O)N(H)—CH₂—CF₃)— Ib-b370

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b371

—CH(OH)— Ib-b372

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b373

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b374

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b375

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b376

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b377

—N(C(O)N(H)—CH₂—CF₃)— Ib-b378

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b379

—CH(OH)— Ib-b380

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b381

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b382

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b383

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b384

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b385

—N(C(O)N(H)—CH₂—CF₃)— Ib-b386

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b387

—CH(OH)— Ib-b388

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b389

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b390

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b391

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b392

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b393

—N(C(O)N(H)—CH₂—CF₃)— Ib-b394

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b395

—CH(OH)— Ib-b396

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b397

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b398

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b399

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b400

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b401

—N(C(O)N(H)—CH₂—CF₃)— Ib-b402

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b403

—CH(OH)— Ib-b404

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b405

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b406

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b407

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b408

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b409

—N(C(O)N(H)—CH₂—CF₃)— Ib-b410

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b411

—CH(OH)— Ib-b412

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b413

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b414

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b415

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b416

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b417

—N(C(O)N(H)—CH₂—CF₃)— Ib-b418

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b419

—CH(OH)— Ib-b420

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b421

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b422

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b423

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b424

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b425

—N(C(O)N(H)—CH₂—CF₃)— Ib-b426

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b427

—CH(OH)— Ib-b428

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b429

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b430

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b431

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b432

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b433

—N(C(O)N(H)—CH₂—CF₃)— Ib-b434

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b435

—CH(OH)— Ib-b436

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b437

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b438

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b439

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b440

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b441

—N(C(O)N(H)—CH₂—CF₃)— Ib-b442

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b443

—CH(OH)— Ib-b444

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b445

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b446

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b447

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b448

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b449

—N(C(O)N(H)—CH₂—CF₃)— Ib-b450

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b451

—CH(OH)— Ib-b452

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b453

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b454

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b455

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b456

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b457

—N(C(O)N(H)—CH₂—CF₃)— Ib-b458

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b459

—CH(OH)— Ib-b460

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b461

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b462

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b463

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b464

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b465

—N(C(O)N(H)—CH₂—CF₃)— Ib-b466

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b467

—CH(OH)— Ib-b468

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b469

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b470

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b471

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b472

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b473

N(C(O)N(H)—CH₂—CF₃)— Ib-b474

N(C(O)N(H)—(CH₂)₃—OH)— Ib-b475

—CH(OH)— Ib-b476

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b477

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b478

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b479

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b480

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b481

N(C(O)N(H)—CH₂—CF₃)— Ib-b482

N(C(O)N(H)—(CH₂)₃—OH)— Ib-b483

—CH(OH)— Ib-b484

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b485

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b486

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b487

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b488

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b489

N(C(O)N(H)—CH₂—CF₃)— Ib-b490

N(C(O)N(H)—(CH₂)₃—OH)— Ib-b491 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —CH(OH)— Ib-b492—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b493—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b494—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b495—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b496—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b497—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CF₃)— Ib-b498—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b499—CH₂—CH₂—CH₂—OS(O)₂OH —CH(OH)— Ib-b500 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b501 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b502 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b503 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b504 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b505 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CF₃)— Ib-b506 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b507

—CH(OH)— Ib-b508

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b509

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b510

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b511

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b512

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b513

—N(C(O)N(H)—CH₂—CF₃)— Ib-b514

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b515

—CH(OH)— Ib-b516

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b517

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b518

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b519

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b520

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b521

—N(C(O)N(H)—CH₂—CF₃)— Ib-b522

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b523 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)—Ib-b524 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b525—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b526—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b527—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b528—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b529—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ib-b530—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b531—CH₂—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)— Ib-b532 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b533 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b534 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b535 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b536 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b537 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CF₃)— Ib-b538 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b539

—CH(OH)— Ib-b540

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b541

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b542

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b543

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b544

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b545

—N(C(O)N(H)—CH₂—CF₃)— Ib-b546

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b547

—CH(OH)— Ib-b548

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b549

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b550

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b551

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b552

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b553

—N(C(O)N(H)—CH₂—CF₃)— Ib-b554

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b555

—CH(OH)— Ib-b556

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b557

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b558

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b559

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b560

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b561

—N(C(O)N(H)—CH₂—CF₃)— Ib-b562

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b563

—CH(OH)— Ib-b564

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b565

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b566

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b567

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b568

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b569

—N(C(O)N(H)—CH₂—CF₃)— Ib-b570

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b571

—CH(OH)— Ib-b572

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b573

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b574

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b575

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b576

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b577

—N(C(O)N(H)—CH₂—CF₃)— Ib-b578

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b579

—CH(OH)— Ib-b580

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b581

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b582

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b583

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b584

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b585

—N(C(O)N(H)—CH₂—CF₃)— Ib-b586

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b587

—CH(OH)— Ib-b588

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b589

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b590

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b591

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b592

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b593

—N(C(O)N(H)—CH₂—CF₃)— Ib-b594

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b595

—CH(OH)— Ib-b596

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b597

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b598

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b599

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b600

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b601

—N(C(O)N(H)—CH₂—CF₃)— Ib-b602

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b603

—CH(OH)— Ib-b604

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b605

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b606

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b607

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b608

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b609

—N(C(O)N(H)—CH₂—CF₃)— Ib-b610

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b611 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —CH(OH)—Ib-b612 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b613—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b614—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b615—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b616—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b617—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ib-b618—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b619

—CH(OH)— Ib-b620

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b621

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b622

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b623

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b624

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b625

—N(C(O)N(H)—CH₂—CF₃)— Ib-b626

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b627

—CH(OH)— Ib-b628

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b629

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b630

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b631

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b632

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b633

—N(C(O)N(H)—CH₂—CF₃)— Ib-b634

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b635

—CH(OH)— Ib-b636

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b637

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b638

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b639

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b640

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b641

—N(C(O)N(H)—CH₂—CF₃)— Ib-b642

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b643

—CH(OH)— Ib-b644

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b645

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b646

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b647

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b648

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b649

—N(C(O)N(H)—CH₂—CF₃)— Ib-b650

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b651

—CH(OH)— Ib-b652

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b653

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b654

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b655

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b656

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b657

—N(C(O)N(H)—CH₂—CF₃)— Ib-b658

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b659

—CH(OH)— Ib-b660

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b661

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b662

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b663

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b664

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b665

—N(C(O)N(H)—CH₂—CF₃)— Ib-b666

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b667

—CH(OH)— Ib-b668

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b669

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b670

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b671

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b672

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b673

—N(C(O)N(H)—CH₂—CF₃)— Ib-b674

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b675

—CH(OH)— Ib-b676

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b677

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b678

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b679

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b680

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b681

—N(C(O)N(H)—CH₂—CF₃)— Ib-b682

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b683

—CH(OH)— Ib-b684

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b685

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b686

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b687

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b688

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b689

—N(C(O)N(H)—CH₂—CF₃)— Ib-b690

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b691

—CH(OH)— Ib-b692

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b693

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b694

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b695

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b696

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b697

—N(C(O)N(H)—CH₂—CF₃)— Ib-b698

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b699

—CH(OH)— Ib-b700

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b701

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b702

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b703

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b704

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b705

—N(C(O)N(H)—CH₂—CF₃)— Ib-b706

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b707

—CH(OH)— Ib-b708

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b709

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b710

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b711

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b712

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b713

—N(C(O)N(H)—CH₂—CF₃)— Ib-b714

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b715

—CH(OH)— Ib-b716

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b717

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b718

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b719

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b720

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b721

—N(C(O)N(H)—CH₂—CF₃)— Ib-b722

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b723

—CH(OH)— Ib-b724

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b725

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b726

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b727

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b728

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b729

—N(C(O)N(H)—CH₂—CF₃)— Ib-b730

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b731

—CH(OH)— Ib-b732

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b733

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b734

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b735

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b736

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b737

—N(C(O)N(H)—CH₂—CF₃)— Ib-b738

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b739

—CH(OH)— Ib-b740

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b741

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b742

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b743

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b744

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b745

—N(C(O)N(H)—CH₂—CF₃)— Ib-b746

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b747

—CH(OH)— Ib-b748

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b749

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b750

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b751

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b752

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b753

—N(C(O)N(H)—CH₂—CF₃)— Ib-b754

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b755

—CH(OH)— Ib-b756

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b757

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b758

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b759

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b760

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b761

—N(C(O)N(H)—CH₂—CF₃)— Ib-b762

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b763

—CH(OH)— Ib-b764

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b765

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b766

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b767

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b768

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b769

—N(C(O)N(H)—CH₂—CF₃)— Ib-b770

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b771

—CH(OH)— Ib-b772

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b773

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b774

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b775

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b776

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b777

—N(C(O)N(H)—CH₂—CF₃)— Ib-b778

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b779 —CH₂—NH—CH₃ —CH(OH)— Ib-b780 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b781 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)—Ib-b782 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b783 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b784 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)—Ib-b785 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ib-b786 —CH₂—NH—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b787 —CH₂—NH—CH₂—CH₃ —CH(OH)— Ib-b788—CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b789 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b790 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b791 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b792 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b793 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CF₃)—Ib-b794 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b795—CH₂—NH—CH₂—CH₂—CH₃ —CH(OH)— Ib-b796 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b797 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b798 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b799 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b800 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b801 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CF₃)— Ib-b802 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b803

—CH(OH)— Ib-b804

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b805

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b806

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b807

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b808

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b809

—N(C(O)N(H)—CH₂—CF₃)— Ib-b810

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b811

—CH(OH)— Ib-b812

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b813

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b814

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b815

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b816

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b817

N(C(O)N(H)—CH₂—CF₃)— Ib-b818

N(C(O)N(H)—(CH₂)₃—OH)— Ib-b819

—CH(OH)— Ib-b820

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b821

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b822

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b823

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b824

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b825

—N(C(O)N(H)—CH₂—CF₃)— Ib-b826

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b827

—CH(OH)— Ib-b828

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b829

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b830

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b831

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b832

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b833

—N(C(O)N(H)—CH₂—CF₃)— Ib-b834

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b835

—CH(OH)— Ib-b836

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b837

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b838

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b839

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b840

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b841

—N(C(O)N(H)—CH₂—CF₃)— Ib-b842

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b843

—CH(OH)— Ib-b844

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b845

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b846

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b847

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b848

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b849

—N(C(O)N(H)—CH₂—CF₃)— Ib-b850

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b851

—CH(OH)— Ib-b852

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b853

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b854

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b855

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b856

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b857

—N(C(O)N(H)—CH₂—CF₃)— Ib-b858

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b859

—CH(OH)— Ib-b860

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b861

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b862

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b863

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b864

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b865

—N(C(O)N(H)—CH₂—CF₃)— Ib-b866

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b867

—CH(OH)— Ib-b868

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b869

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b870

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b871

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b872

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b873

—N(C(O)N(H)—CH₂—CF₃)— Ib-b874

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b875

—CH(OH)— Ib-b876

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b877

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b878

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b879

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b880

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b881

—N(C(O)N(H)—CH₂—CF₃)— Ib-b882

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b883

—CH(OH)— Ib-b884

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b885

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b886

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b887

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b888

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b889

—N(C(O)N(H)—CH₂—CF₃)— Ib-b890

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b891

—CH(OH)— Ib-b892

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b893

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b894

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b895

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b896

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b897

—N(C(O)N(H)—CH₂—CF₃)— Ib-b898

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b899

—CH(OH)— Ib-b900

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b901

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b902

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b903

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b904

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b905

—N(C(O)N(H)—CH₂—CF₃)— Ib-b906

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b907

—CH(OH)— Ib-b908

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b909

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b910

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b911

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b912

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b913

—N(C(O)N(H)—CH₂—CF₃)— Ib-b914

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b915

—CH(OH)— Ib-b916

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b917

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b918

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b919

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b920

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b921

—N(C(O)N(H)—CH₂—CF₃)— Ib-b922

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b923

—CH(OH)— Ib-b924

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b925

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b926

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b927

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b928

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b929

—N(C(O)N(H)—CH₂—CF₃)— Ib-b930

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b931

—CH(OH)— Ib-b932

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b933

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b934

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b935

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b936

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b937

—N(C(O)N(H)—CH₂—CF₃)— Ib-b938

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b939

—CH(OH)— Ib-b940

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b941

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b942

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b943

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b944

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b945

—N(C(O)N(H)—CH₂—CF₃)— Ib-b946

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b947

—CH(OH)— Ib-b948

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b949

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b950

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b951

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b952

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b953

—N(C(O)N(H)—CH₂—CF₃)— Ib-b954

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b955

—CH(OH)— Ib-b956

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b957

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b958

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b959

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b960

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b961

—N(C(O)N(H)—CH₂—CF₃)— Ib-b962

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b963 —CH₂—N(CH₂CH₃)(CH₃) —CH(OH)— Ib-b964—CH₂—N(CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b965 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b966 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b967 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b968 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b969 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ib-b970 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b971 —CH₂—N(CH₂CH₂CH₃)(CH₃) —CH(OH)— Ib-b972—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b973—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b974—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b975—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b976—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b977—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CF₃)— Ib-b978—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—(CH₂)₃—OH)— Ib-b979—CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃) —CH(OH)— Ib-b980 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b981 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b982 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b983 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b984 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b985 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ib-b986 —CH₂——N(CH₂CH₂CH₂CH₃)—(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b987 —CH₂—NH—CH₂CH₂CH₂CH₃ —CH(OH)— Ib-b988—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b989—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b990—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b991—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b992—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b993—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ib-b994 —CH₂—NH—CH₂CH₂CH₂CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b995 —CH₂—NH—CH₂CH₂—O—CH₃ —CH(OH)— Ib-b996—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b997—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ib-b998—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b999—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1000—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1001—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ib-b1002 —CH₂—NH—CH₂CH₂—O—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1003

—CH(OH)— Ib-b1004

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1005

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1006

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1007

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1008

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1009

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1010

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1011

—CH(OH)— Ib-b1012

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1013

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1014

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1015

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1016

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1017

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1018

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1019

—CH(OH)— Ib-b1020

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1021

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1022

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1023

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1024

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1025

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1026

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1027

—CH(OH)— Ib-b1028

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1029

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1030

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1031

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1032

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1033

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1034

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1035

—CH(OH)— Ib-b1036

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1037

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1038

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1039

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1040

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1041

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1042

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1043

—CH(OH)— Ib-b1044

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1045

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1046

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1047

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1048

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1049

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1050

—N(C(O)N(H)—(CH₂)₃—OH)— Ib-b1051

—CH(OH)— Ib-b1052

—N(C(O)N(H)—CH₂—CH₂—OH)— Ib-b1053

—N(C(O)N(H)—CH₂—CH₂—F)— Ib-b1054

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ib-b1055

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1056

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ib-b1057

—N(C(O)N(H)—CH₂—CF₃)— Ib-b1058

—N(C(O)N(H)—(CH₂)₃—OH)—

and pharmaceutically acceptable salts thereof.

5.4 The Indenoisoquinolinone Analogs of Formula (Ic)

The present invention provides Indenoisoquinolinone Analogs according toFormula (Ic), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (Ic).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂ CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —(CH₂)_(n)—N(R²)(R²) and X is —N(C(CH₃)₃)—.

In one embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(CH₂C(H)(CH₃)₂)—.

In another embodiment, R¹ is —O—(CH₂)_(m)—N(R²)(R²) and X is—N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In one embodiment, X is —CH(OH)—.

In another embodiment, X is —CH(OH)— and R¹ is —(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —CH(OH)— and R¹ is —(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)-Z)- and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OH)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—F)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and R¹ is—(CH₂)— N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)₂—OMe)- and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)_(n)—N(R²)(R²).

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In still another embodiment, X is —N((CH₂)—CF₃)— and R¹ is—(CH₂)—N(R²)(R²).

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, m is 2.

In another embodiment, m is 3.

In yet another embodiment, m is 4, 5, or 6.

In a further embodiment, m is 7, 8, or 9.

In yet a further embodiment, m is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is —N(CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₃)(CH₃),

—N(CH₂CH₂CH₂CH₃)(CH₃),

—NH—CH₂CH₂CH₂CH₃, or

—NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—;

R¹ is —(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²);

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl;

n is an integer ranging from 1 to 10; and

m is an integer ranging from 2 to 10.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at least one R² is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at least one R² is —C₃-C₈monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; R¹ is —CH₂—N(R²)(R²); and at leastone R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein N and both R² groupsare taken together to form a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, which is substituted with a hydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and R¹ is —CH₂—N(R²)(R²), wherein Nand both R² groups are taken together to form a nitrogen-containing 3-to 7-membered monocyclic heterocycle, which is substituted with anitrogen-containing 3- to 7-membered monocyclic heterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (Ic) as set forth below:

(Ic)

Compound n —R¹ X Ic-1 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-2 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-3 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-4 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-5 5 —(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-6 6—(CH₂)_(n)—N(CH₃)₂ —N(CH₃)— Ic-7 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ic-8 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ic-9 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)—Ic-10 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ic-11 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₃)— Ic-12 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₃)— Ic-13 1—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-14 2 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ic-15 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-16 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-17 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ic-18 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-19 1—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-20 2 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ic-21 3 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-22 4—(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-23 5 —(CH₂)_(n)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ic-24 6 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-25 1—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-26 2 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ic-27 3 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ic-28 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-29 5—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-30 6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)(CH₂CH₃))— Ic-31 1 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-322 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-33 3 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ic-34 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-35 5—(CH₂)_(n)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-36 6 —(CH₂)_(n)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ic-37 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-38 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-39 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ic-40 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-41 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-42 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ic-43 1 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ic-44 2—(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ic-45 3 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)—Ic-46 4 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ic-47 5 —(CH₂)_(n)—N(CH₃)₂—N(C(CH₃)₃)— Ic-48 6 —(CH₂)_(n)—N(CH₃)₂ —N(C(CH₃)₃)— Ic-49 1

—N(CH₃)— Ic-50 2

—N(CH₃)— Ic-51 3

—N(CH₃)— Ic-52 4

—N(CH₃)— Ic-53 5

—N(CH₃)— Ic-54 6

—N(CH₃)— Ic-55 1

—N(CH₂CH₃)— Ic-56 2

—N(CH₂CH₃)— Ic-57 3

—N(CH₂CH₃)— Ic-58 4

—N(CH₂CH₃)— Ic-59 5

—N(CH₂CH₃)— Ic-60 6

—N(CH₂CH₃)— Ic-61 1

—N(CH₂CH₂CH₃)— Ic-62 2

—N(CH₂CH₂CH₃)— Ic-63 3

—N(CH₂CH₂CH₃)— Ic-64 4

—N(CH₂CH₂CH₃)— Ic-65 5

—N(CH₂CH₂CH₃)— Ic-66 6

—N(CH₂CH₂CH₃)— Ic-67 1

—N(CH₂CH₂CH₂CH₃)— Ic-68 2

—N(CH₂CH₂CH₂CH₃)— Ic-69 3

—N(CH₂CH₂CH₂CH₃)— Ic-70 4

—N(CH₂CH₂CH₂CH₃)— Ic-71 5

—N(CH₂CH₂CH₂CH₃)— Ic-72 6

—N(CH₂CH₂CH₂CH₃)— Ic-73 1

—N(C(H)(CH₃)(CH₂CH₃))— Ic-74 2

—N(C(H)(CH₃)(CH₂CH₃))— Ic-75 3

—N(C(H)(CH₃)(CH₂CH₃))— Ic-76 4

—N(C(H)(CH₃)(CH₂CH₃))— Ic-77 5

—N(C(H)(CH₃)(CH₂CH₃))— Ic-78 6

—N(C(H)(CH₃)(CH₂CH₃))— Ic-79 1

—N(C(H)(CH₃)₂)— Ic-80 2

—N(C(H)(CH₃)₂)— Ic-81 3

—N(C(H)(CH₃)₂)— Ic-82 4

—N(C(H)(CH₃)₂)— Ic-83 5

—N(C(H)(CH₃)₂)— Ic-84 6

—N(C(H)(CH₃)₂)— Ic-85 1

—N(CH₂C(H)(CH₃)₂)— Ic-86 2

—N(CH₂C(H)(CH₃)₂)— Ic-87 3

—N(CH₂C(H)(CH₃)₂)— Ic-88 4

—N(CH₂C(H)(CH₃)₂)— Ic-89 5

—N(CH₂C(H)(CH₃)₂)— Ic-90 6

—N(CH₂C(H)(CH₃)₂)— Ic-91 1

—N(C(CH₃)₃)— Ic-92 2

—N(C(CH₃)₃)— Ic-93 3

—N(C(CH₃)₃)— Ic-94 4

—N(C(CH₃)₃)— Ic-95 5

—N(C(CH₃)₃)— Ic-96 6

—N(C(CH₃)₃)— Compound m —R¹ X Ic-146 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ic-147 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ic-148 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₃)— Ic-149 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ic-150 6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)— Ic-151 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₃)—Ic-152 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ic-153 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ic-154 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ic-155 6—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ic-156 2 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₃)— Ic-157 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₃)— Ic-158 4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-159 5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ic-160 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-161 2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-162 3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₃)— Ic-163 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-164 5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-165 6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ic-166 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-1673 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-168 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ic-169 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-1706 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-171 2—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-172 3—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-173 4—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-174 5—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-175 6—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-176 2—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-178 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ic-179 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-180 5—O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-181 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(H)(CH₃)₂)— Ic-182 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-183 3—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-184 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂C(H)(CH₃)₂)— Ic-185 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)—Ic-186 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-187 2

—N(CH₃)— Ic-188 3

—N(CH₃)— Ic-189 4

—N(CH₃)— Ic-190 5

—N(CH₃)— Ic-191 6

—N(CH₃)— Ic-192 2

—N(CH₃)— Ic-193 3

—N(CH₂CH₃)— Ic-194 4

—N(CH₂CH₃)— Ic-195 5

—N(CH₂CH₃)— Ic-196 6

—N(CH₂CH₃)— Ic-197 2

—N(CH₂CH₃)— Ic-198 3

—N(CH₂CH₃)— Ic-199 4

—N(CH₂CH₂CH₃)— Ic-200 5

—N(CH₂CH₂CH₃)— Ic-201 6

—N(CH₂CH₂CH₃)— Ic-202 2

—N(CH₂CH₂CH₃)— Ic-203 3

—N(CH₂CH₂CH₃)— Ic-204 4

—N(CH₂CH₂CH₃)— Ic-205 5

—N(CH₂CH₂CH₂CH₃)— Ic-206 6

—N(CH₂CH₂CH₂CH₃)— Ic-207 2

—N(CH₂CH₂CH₂CH₃)— Ic-208 3

—N(CH₂CH₂CH₂CH₃)— Ic-209 4

—N(CH₂CH₂CH₂CH₃)— Ic-210 5

—N(CH₂CH₂CH₂CH₃)— Ic-211 6

—N(C(H)(CH₃)(CH₂CH₃))— Ic-212 2

—N(C(H)(CH₃)(CH₂CH₃))— Ic-213 3

—N(C(H)(CH₃)(CH₂CH₃))— Ic-214 4

—N(C(H)(CH₃)(CH₂CH₃))— Ic-215 5

—N(C(H)(CH₃)(CH₂CH₃))— Ic-216 6

—N(C(H)(CH₃)(CH₂CH₃))— Ic-217 2

—N(C(H)(CH₃)₂)— Ic-218 3

—N(C(H)(CH₃)₂)— Ic-219 4

—N(C(H)(CH₃)₂)— Ic-220 5

—N(C(H)(CH₃)₂)— Ic-221 6

—N(C(H)(CH₃)₂)— Ic-222 2

—N(C(H)(CH₃)₂)— Ic-223 3

—N(CH₂C(H)(CH₃)₂)— Ic-224 4

—N(CH₂C(H)(CH₃)₂)— Ic-225 5

—N(CH₂C(H)(CH₃)₂)— Ic-226 6

—N(CH₂C(H)(CH₃)₂)— Compound —R¹ X Ic-267 —CH₂—N(CH₂—CH₃)₂ —N(CH₃)—Ic-268 —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₃)— Ic-269 —CH₂—N(CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ic-270 —CH₂—N(CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-271—CH₂—N(CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-272 —CH₂—N(CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ic-273 —CH₂—N(CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-274—CH₂—N(CH₂—CH₃)₂ —N(C(CH₃)₃)— Ic-275 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₃)—Ic-276 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₃)— Ic-277 —CH₂—N(CH₂—CH₂—CH₃)₂—N(CH₂CH₂CH₃)— Ic-278 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-279—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-280 —CH₂—N(CH₂—CH₂—CH₃)₂—N(C(H)(CH₃)₂)— Ic-281 —CH₂—N(CH₂—CH₂—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-282—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(CH₃)₃)— Ic-283 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₃)—Ic-284 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₃)— Ic-285 —CH₂—N(CH₂—CH₂OH)₂—N(CH₂CH₂CH₃)— Ic-286 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂CH₂CH₂CH₃)— Ic-287—CH₂—N(CH₂—CH₂OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-288 —CH₂—N(CH₂—CH₂OH)₂—N(C(H)(CH₃)₂)— Ic-289 —CH₂—N(CH₂—CH₂OH)₂ —N(CH₂C(H)(CH₃)₂)— Ic-290—CH₂—N(CH₂—CH₂OH)₂ —N(C(CH₃)₃)— Ic-291 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₃)—Ic-292 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₃)— Ic-293—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ic-294 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂—N(CH₂CH₂CH₂CH₃)— Ic-295 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ic-296 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)₂)— Ic-297—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)— Ic-298—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(CH₃)₃)— Ic-299—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₃)— Ic-300—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₃)— Ic-301—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₃)— Ic-302—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂CH₂CH₂CH₃)— Ic-303—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-304—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(H)(CH₃)₂)— Ic-305—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(CH₂C(H)(CH₃)₂)— Ic-306—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(CH₃)₃)— Ic-307

—N(CH₃)— Ic-308

—N(CH₂CH₃)— Ic-309

—N(CH₂CH₂CH₃)— Ic-310

—N(CH₂CH₂CH₂CH₃)— Ic-311

—N(C(H)(CH₃)(CH₂CH₃))— Ic-312

—N(C(H)(CH₃)₂)— Ic-313

—N(CH₂C(H)(CH₃)₂)— Ic-314

—N(C(CH₃)₃)— Ic-315

—N(CH₃)— Ic-316

—N(CH₂CH₃)— Ic-317

—N(CH₂CH₂CH₃)— Ic-318

—N(CH₂CH₂CH₂CH₃)— Ic-319

—N(C(H)(CH₃)(CH₂CH₃))— Ic-320

—N(C(H)(CH₃)₂)— Ic-321

—N(CH₂C(H)(CH₃)₂)— Ic-322

—N(C(CH₃)₃)— Ic-323

—N(CH₃)— Ic-324

—N(CH₂CH₃)— Ic-325

—N(CH₂CH₂CH₃)— Ic-326

—N(CH₂CH₂CH₂CH₃)— Ic-327

—N(C(H)(CH₃)(CH₂CH₃))— Ic-328

—N(C(H)(CH₃)₂)— Ic-329

—N(CH₂C(H)(CH₃)₂)— Ic-330

—N(C(CH₃)₃)— Ic-331

—N(CH₃)— Ic-332

—N(CH₂CH₃)— Ic-333

—N(CH₂CH₂CH₃)— Ic-334

—N(CH₂CH₂CH₂CH₃)— Ic-335

—N(C(H)(CH₃)(CH₂CH₃))— Ic-336

—N(C(H)(CH₃)₂)— Ic-337

—N(CH₂C(H)(CH₃)₂)— Ic-338

—N(C(CH₃)₃)— Ic-339

—N(CH₃)— Ic-340

—N(CH₂CH₃)— Ic-341

—N(CH₂CH₂CH₃)— Ic-342

—N(CH₂CH₂CH₂CH₃)— Ic-343

—N(C(H)(CH₃)(CH₂CH₃))— Ic-344

—N(C(H)(CH₃)₂)— Ic-345

—N(CH₂C(H)(CH₃)₂)— Ic-346

—N(C(CH₃)₃)— Ic-347

—N(CH₃)— Ic-348

—N(CH₂CH₃)— Ic-349

—N(CH₂CH₂CH₃)— Ic-350

—N(CH₂CH₂CH₂CH₃)— Ic-351

—N(C(H)(CH₃)(CH₂CH₃))— Ic-352

—N(C(H)(CH₃)₂)— Ic-353

—N(CH₂C(H)(CH₃)₂)— Ic-354

—N(C(CH₃)₃)— Ic-355

—N(CH₃)— Ic-356

—N(CH₂CH₃)— Ic-357

—N(CH₂CH₂CH₃)— Ic-358

—N(CH₂CH₂CH₂CH₃)— Ic-359

—N(C(H)(CH₃)(CH₂CH₃))— Ic-360

—N(C(H)(CH₃)₂)— Ic-361

—N(CH₂C(H)(CH₃)₂)— Ic-362

—N(C(CH₃)₃)— Ic-363

—N(CH₃)— Ic-364

—N(CH₂CH₃)— Ic-365

—N(CH₂CH₂CH₃)— Ic-366

—N(CH₂CH₂CH₂CH₃)— Ic-367

—N(C(H)(CH₃)(CH₂CH₃))— Ic-368

—N(C(H)(CH₃)₂)— Ic-369

—N(CH₂C(H)(CH₃)₂)— Ic-370

—N(C(CH₃)₃)— Ic-371

—N(CH₃)— Ic-372

—N(CH₂CH₃)— Ic-373

—N(CH₂CH₂CH₃)— Ic-374

—N(CH₂CH₂CH₂CH₃)— Ic-375

—N(C(H)(CH₃)(CH₂CH₃))— Ic-376

—N(C(H)(CH₃)₂)— Ic-377

—N(CH₂C(H)(CH₃)₂)— Ic-378

—N(C(CH₃)₃)— Ic-379

—N(CH₃)— Ic-380

—N(CH₂CH₃)— Ic-381

—N(CH₂CH₂CH₃)— Ic-382

—N(CH₂CH₂CH₂CH₃)— Ic-383

—N(C(H)(CH₃)(CH₂CH₃))— Ic-384

—N(C(H)(CH₃)₂)— Ic-385

—N(CH₂C(H)(CH₃)₂)— Ic-386

—N(C(CH₃)₃)— Ic-387

—N(CH₃)— Ic-388

—N(CH₂CH₃)— Ic-389

—N(CH₂CH₂CH₃)— Ic-390

—N(CH₂CH₂CH₂CH₃)— Ic-391

—N(C(H)(CH₃)(CH₂CH₃))— Ic-392

—N(C(H)(CH₃)₂)— Ic-393

—N(CH₂C(H)(CH₃)₂)— Ic-394

—N(C(CH₃)₃)— Ic-395

—N(CH₃)— Ic-396

—N(CH₂CH₃)— Ic-397

—N(CH₂CH₂CH₃)— Ic-398

—N(CH₂CH₂CH₂CH₃)— Ic-399

—N(C(H)(CH₃)(CH₂CH₃))— Ic-400

—N(C(H)(CH₃)₂)— Ic-401

—N(CH₂C(H)(CH₃)₂)— Ic-402

—N(C(CH₃)₃)— Ic-403

—N(CH₃)— Ic-404

—N(CH₂CH₃)— Ic-405

—N(CH₂CH₂CH₃)— Ic-406

—N(CH₂CH₂CH₂CH₃)— Ic-407

—N(C(H)(CH₃)(CH₂CH₃))— Ic-408

—N(C(H)(CH₃)₂)— Ic-409

—N(CH₂C(H)(CH₃)₂)— Ic-410

—N(C(CH₃)₃)— Ic-411

—N(CH₃)— Ic-412

—N(CH₂CH₃)— Ic-413

—N(CH₂CH₂CH₃)— Ic-414

—N(CH₂CH₂CH₂CH₃)— Ic-415

—N(C(H)(CH₃)(CH₂CH₃))— Ic-416

—N(C(H)(CH₃)₂)— Ic-417

—N(CH₂C(H)(CH₃)₂)— Ic-418

—N(C(CH₃)₃)— Ic-419

—N(CH₃)— Ic-420

—N(CH₂CH₃)— Ic-421

—N(CH₂CH₂CH₃)— Ic-422

—N(CH₂CH₂CH₂CH₃)— Ic-423

—N(C(H)(CH₃)(CH₂CH₃))— Ic-424

—N(C(H)(CH₃)₂)— Ic-425

—N(CH₂C(H)(CH₃)₂)— Ic-426

—N(C(CH₃)₃)— Ic-427

—N(CH₃)— Ic-428

—N(CH₂CH₃)— Ic-429

—N(CH₂CH₂CH₃)— Ic-430

—N(CH₂CH₂CH₂CH₃)— Ic-431

—N(C(H)(CH₃)(CH₂CH₃))— Ic-432

—N(C(H)(CH₃)₂)— Ic-433

—N(CH₂C(H)(CH₃)₂)— Ic-434

—N(C(CH₃)₃)— Ic-435

—N(CH₃)— Ic-436

—N(CH₂CH₃)— Ic-437

—N(CH₂CH₂CH₃)— Ic-438

—N(CH₂CH₂CH₂CH₃)— Ic-439

—N(C(H)(CH₃)(CH₂CH₃))— Ic-440

—N(C(H)(CH₃)₂)— Ic-441

—N(CH₂C(H)(CH₃)₂)— Ic-442

—N(C(CH₃)₃)— Ic-443

—N(CH₃)— Ic-444

—N(CH₂CH₃)— Ic-445

—N(CH₂CH₂CH₃)— Ic-446

—N(CH₂CH₂CH₂CH₃)— Ic-447

—N(C(H)(CH₃)(CH₂CH₃))— Ic-448

—N(C(H)(CH₃)₂)— Ic-449

—N(CH₂C(H)(CH₃)₂)— Ic-450

—N(C(CH₃)₃)— Ic-451

—N(CH₃)— Ic-452

—N(CH₂CH₃)— Ic-453

—N(CH₂CH₂CH₃)— Ic-454

—N(CH₂CH₂CH₂CH₃)— Ic-455

—N(C(H)(CH₃)(CH₂CH₃))— Ic-456

—N(C(H)(CH₃)₂)— Ic-457

—N(CH₂C(H)(CH₃)₂)— Ic-458

—N(C(CH₃)₃)— Ic-459

—N(CH₃)— Ic-460

—N(CH₂CH₃)— Ic-461

—N(CH₂CH₂CH₃)— Ic-462

—N(CH₂CH₂CH₂CH₃)— Ic-463

—N(C(H)(CH₃)(CH₂CH₃))— Ic-464

—N(C(H)(CH₃)₂)— Ic-465

—N(CH₂C(H)(CH₃)₂)— Ic-466

—N(C(CH₃)₃)— Ic-467

—N(CH₃)— Ic-468

—N(CH₂CH₃)— Ic-469

—N(CH₂CH₂CH₃)— Ic-470

—N(CH₂CH₂CH₂CH₃)— Ic-471

—N(C(H)(CH₃)(CH₂CH₃))— Ic-472

—N(C(H)(CH₃)₂)— Ic-473

—N(CH₂C(H)(CH₃)₂)— Ic-474

—N(C(CH₃)₃)— Ic-475

—N(CH₃)— Ic-476

—N(CH₂CH₃)— Ic-477

—N(CH₂CH₂CH₃)— Ic-478

—N(CH₂CH₂CH₂CH₃)— Ic-479

—N(C(H)(CH₃)(CH₂CH₃))— Ic-480

—N(C(H)(CH₃)₂)— Ic-481

—N(CH₂C(H)(CH₃)₂)— Ic-482

—N(C(CH₃)₃)— Ic-483

—N(CH₃)— Ic-484

—N(CH₂CH₃)— Ic-485

—N(CH₂CH₂CH₃)— Ic-486

—N(CH₂CH₂CH₂CH₃)— Ic-487

—N(C(H)(CH₃)(CH₂CH₃))— Ic-488

—N(C(H)(CH₃)₂)— Ic-489

—N(CH₂C(H)(CH₃)₂)— Ic-490

—N(C(CH₃)₃)— Ic-491 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₃)— Ic-492—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₃)— Ic-493 —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂CH₂CH₃)— Ic-494 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(CH₂CH₂CH₂CH₃)— Ic-495—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-496—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(H)(CH₃)₂)— Ic-497 —CH₂—CH₂—CH₂—OP(O)(OH)₂—N(CH₂C(H)(CH₃)₂)— Ic-498 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(CH₃)₃)— Ic-499—CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₃)— Ic-500 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₃)—Ic-501 —CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂CH₂CH₃)— Ic-502 —CH₂—CH₂—CH₂—OS(O)₂OH—N(CH₂CH₂CH₂CH₃)— Ic-503 —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(H)(CH₃)(CH₂CH₃))—Ic-504 —CH₂—CH₂—CH₂—OS(O)₂OH —N(C(H)(CH₃)₂)— Ic-505—CH₂—CH₂—CH₂—OS(O)₂OH —N(CH₂C(H)(CH₃)₂)— Ic-506 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(CH₃)₃)— Ic-507

—N(CH₃)— Ic-508

—N(CH₂CH₃)— Ic-509

—N(CH₂CH₂CH₃)— Ic-510

—N(CH₂CH₂CH₂CH₃)— Ic-511

—N(C(H)(CH₃)(CH₂CH₃))— Ic-512

—N(C(H)(CH₃)₂)— Ic-513

—N(CH₂C(H)(CH₃)₂)— Ic-514

—N(C(CH₃)₃)— Ic-515

—N(CH₃)— Ic-516

—N(CH₂CH₃)— Ic-517

—N(CH₂CH₂CH₃)— Ic-518

—N(CH₂CH₂CH₂CH₃)— Ic-519

—N(C(H)(CH₃)(CH₂CH₃))— Ic-520

—N(C(H)(CH₃)₂)— Ic-521

—N(CH₂C(H)(CH₃)₂)— Ic-522

—N(C(CH₃)₃)— Ic-523 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₃)— Ic-524—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ic-525 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂—N(CH₂CH₂CH₃)— Ic-526 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₂CH₃)—Ic-527 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-528—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ic-529—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-530—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(CH₃)₃)— Ic-531 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₃)— Ic-532 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₃)— Ic-533—CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂CH₂CH₃)— Ic-534 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(CH₂CH₂CH₂CH₃)— Ic-535 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))—Ic-536 —CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(C(H)(CH₃)₂)— Ic-537—CH₂—N(CH₂—CH₂—O—CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-538 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(CH₃)₃)— Ic-539

—N(CH₃)— Ic-540

—N(CH₂CH₃)— Ic-541

—N(CH₂CH₂CH₃)— Ic-542

—N(CH₂CH₂CH₂CH₃)— Ic-543

—N(C(H)(CH₃)(CH₂CH₃))— Ic-544

—N(C(H)(CH₃)₂)— Ic-545

—N(CH₂C(H)(CH₃)₂)— Ic-546

—N(C(CH₃)₃)— Ic-547

—N(CH₃)— Ic-548

—N(CH₂CH₃)— Ic-549

—N(CH₂CH₂CH₃)— Ic-550

—N(CH₂CH₂CH₂CH₃)— Ic-551

—N(C(H)(CH₃)(CH₂CH₃))— Ic-552

—N(C(H)(CH₃)₂)— Ic-553

—N(CH₂C(H)(CH₃)₂)— Ic-554

—N(C(CH₃)₃)— Ic-555

—N(CH₃)— Ic-556

—N(CH₂CH₃)— Ic-557

—N(CH₂CH₂CH₃)— Ic-558

—N(CH₂CH₂CH₂CH₃)— Ic-559

—N(C(H)(CH₃)(CH₂CH₃))— Ic-560

—N(C(H)(CH₃)₂)— Ic-561

—N(CH₂C(H)(CH₃)₂)— Ic-562

—N(C(CH₃)₃)— Ic-563

—N(CH₃)— Ic-564

—N(CH₂CH₃)— Ic-565

—N(CH₂CH₂CH₃)— Ic-566

—N(CH₂CH₂CH₂CH₃)— Ic-567

—N(C(H)(CH₃)(CH₂CH₃))— Ic-568

—N(C(H)(CH₃)₂)— Ic-569

—N(CH₂C(H)(CH₃)₂)— Ic-570

—N(C(CH₃)₃)— Ic-571

—N(CH₃)— Ic-572

—N(CH₂CH₃)— Ic-573

—N(CH₂CH₂CH₃)— Ic-574

—N(CH₂CH₂CH₂CH₃)— Ic-575

—N(C(H)(CH₃)(CH₂CH₃))— Ic-576

—N(C(H)(CH₃)₂)— Ic-577

—N(CH₂C(H)(CH₃)₂)— Ic-578

—N(C(CH₃)₃)— Ic-579

—N(CH₃)— Ic-580

—N(CH₂CH₃)— Ic-581

—N(CH₂CH₂CH₃)— Ic-582

—N(CH₂CH₂CH₂CH₃)— Ic-583

—N(C(H)(CH₃)(CH₂CH₃))— Ic-584

—N(C(H)(CH₃)₂)— Ic-585

—N(CH₂C(H)(CH₃)₂)— Ic-586

—N(C(CH₃)₃)— Ic-587

—N(CH₃)— Ic-588

—N(CH₂CH₃)— Ic-589

—N(CH₂CH₂CH₃)— Ic-590

—N(CH₂CH₂CH₂CH₃)— Ic-591

—N(C(H)(CH₃)(CH₂CH₃))— Ic-592

—N(C(H)(CH₃)₂)— Ic-593

—N(CH₂C(H)(CH₃)₂)— Ic-594

—N(C(CH₃)₃)— Ic-595

—N(CH₃)— Ic-596

—N(CH₂CH₃)— Ic-597

—N(CH₂CH₂CH₃)— Ic-598

—N(CH₂CH₂CH₂CH₃)— Ic-599

—N(C(H)(CH₃)(CH₂CH₃))— Ic-600

—N(C(H)(CH₃)₂)— Ic-601

—N(CH₂C(H)(CH₃)₂)— Ic-602

—N(C(CH₃)₃)— Ic-603

—N(CH₃)— Ic-604

—N(CH₂CH₃)— Ic-605

—N(CH₂CH₂CH₃)— Ic-606

—N(CH₂CH₂CH₂CH₃)— Ic-607

—N(C(H)(CH₃)(CH₂CH₃))— Ic-608

—N(C(H)(CH₃)₂)— Ic-609

—N(CH₂C(H)(CH₃)₂)— Ic-610

—N(C(CH₃)₃)— Ic-611 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₃)— Ic-612—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₃)— Ic-613—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₃)— Ic-614—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂CH₂CH₂CH₃)— Ic-615—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)(CH₂CH₃))— Ic-616—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(H)(CH₃)₂)— Ic-617—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(CH₂C(H)(CH₃)₂)— Ic-618—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(CH₃)₃)— Ic-619

—N(CH₃)— Ic-620

—N(CH₂CH₃)— Ic-621

—N(CH₂CH₂CH₃)— Ic-622

—N(CH₂CH₂CH₂CH₃)— Ic-623

—N(C(H)(CH₃)(CH₂CH₃))— Ic-624

—N(C(H)(CH₃)₂)— Ic-625

—N(CH₂C(H)(CH₃)₂)— Ic-626

—N(C(CH₃)₃)— Ic-627

—N(CH₃)— Ic-628

—N(CH₂CH₃)— Ic-629

—N(CH₂CH₂CH₃)— Ic-630

—N(CH₂CH₂CH₂CH₃)— Ic-631

—N(C(H)(CH₃)(CH₂CH₃))— Ic-632

—N(C(H)(CH₃)₂)— Ic-633

—N(CH₂C(H)(CH₃)₂)— Ic-634

—N(C(CH₃)₃)— Ic-635

—N(CH₃)— Ic-636

—N(CH₂CH₃)— Ic-637

—N(CH₂CH₂CH₃)— Ic-638

—N(CH₂CH₂CH₂CH₃)— Ic-639

—N(C(H)(CH₃)(CH₂CH₃))— Ic-640

—N(C(H)(CH₃)₂)— Ic-641

—N(CH₂C(H)(CH₃)₂)— Ic-642

—N(C(CH₃)₃)— Ic-643

—N(CH₃)— Ic-644

—N(CH₂CH₃)— Ic-645

—N(CH₂CH₂CH₃)— Ic-646

—N(CH₂CH₂CH₂CH₃)— Ic-647

—N(C(H)(CH₃)(CH₂CH₃))— Ic-648

—N(C(H)(CH₃)₂)— Ic-649

—N(CH₂C(H)(CH₃)₂)— Ic-650

—N(C(CH₃)₃)— Ic-651

—N(CH₃)— Ic-652

—N(CH₂CH₃)— Ic-653

—N(CH₂CH₂CH₃)— Ic-654

—N(CH₂CH₂CH₂CH₃)— Ic-655

—N(C(H)(CH₃)(CH₂CH₃))— Ic-656

—N(C(H)(CH₃)₂)— Ic-657

—N(CH₂C(H)(CH₃)₂)— Ic-658

—N(C(CH₃)₃)— Ic-659

—N(CH₃)— Ic-660

—N(CH₂CH₃)— Ic-661

—N(CH₂CH₂CH₃)— Ic-662

—N(CH₂CH₂CH₂CH₃)— Ic-663

—N(C(H)(CH₃)(CH₂CH₃))— Ic-664

—N(C(H)(CH₃)₂)— Ic-665

—N(CH₂C(H)(CH₃)₂)— Ic-666

—N(C(CH₃)₃)— Ic-667

—N(CH₃)— Ic-668

—N(CH₂CH₃)— Ic-669

—N(CH₂CH₂CH₃)— Ic-670

—N(CH₂CH₂CH₂CH₃)— Ic-671

—N(C(H)(CH₃)(CH₂CH₃))— Ic-672

—N(C(H)(CH₃)₂)— Ic-673

—N(CH₂C(H)(CH₃)₂)— Ic-674

—N(C(CH₃)₃)— Ic-675

—N(CH₃)— Ic-676

—N(CH₂CH₃)— Ic-677

—N(CH₂CH₂CH₃)— Ic-678

—N(CH₂CH₂CH₂CH₃)— Ic-679

—N(C(H)(CH₃)(CH₂CH₃))— Ic-680

—N(C(H)(CH₃)₂)— Ic-681

—N(CH₂C(H)(CH₃)₂)— Ic-682

—N(C(CH₃)₃)— Ic-683

—N(CH₃)— Ic-684

—N(CH₂CH₃)— Ic-685

—N(CH₂CH₂CH₃)— Ic-686

—N(CH₂CH₂CH₂CH₃)— Ic-687

—N(C(H)(CH₃)(CH₂CH₃))— Ic-688

—N(C(H)(CH₃)₂)— Ic-689

—N(CH₂C(H)(CH₃)₂)— Ic-690

—N(C(CH₃)₃)— Ic-691

—N(CH₃)— Ic-692

—N(CH₂CH₃)— Ic-693

—N(CH₂CH₂CH₃)— Ic-694

—N(CH₂CH₂CH₂CH₃)— Ic-695

—N(C(H)(CH₃)(CH₂CH₃))— Ic-696

—N(C(H)(CH₃)₂)— Ic-697

—N(CH₂C(H)(CH₃)₂)— Ic-698

—N(C(CH₃)₃)— Ic-699

—N(CH₃)— Ic-700

—N(CH₂CH₃)— Ic-701

—N(CH₂CH₂CH₃)— Ic-702

—N(CH₂CH₂CH₂CH₃)— Ic-703

—N(C(H)(CH₃)(CH₂CH₃))— Ic-704

—N(C(H)(CH₃)₂)— Ic-705

—N(CH₂C(H)(CH₃)₂)— Ic-706

—N(C(CH₃)₃)— Ic-707

—N(CH₃)— Ic-708

—N(CH₂CH₃)— Ic-709

—N(CH₂CH₂CH₃)— Ic-710

—N(CH₂CH₂CH₂CH₃)— Ic-711

—N(C(H)(CH₃)(CH₂CH₃))— Ic-712

—N(C(H)(CH₃)₂)— Ic-713

—N(CH₂C(H)(CH₃)₂)— Ic-714

—N(C(CH₃)₃)— Ic-715

—N(CH₃)— Ic-716

—N(CH₂CH₃)— Ic-717

—N(CH₂CH₂CH₃)— Ic-718

—N(CH₂CH₂CH₂CH₃)— Ic-719

—N(C(H)(CH₃)(CH₂CH₃))— Ic-720

—N(C(H)(CH₃)₂)— Ic-721

—N(CH₂C(H)(CH₃)₂)— Ic-722

—N(C(CH₃)₃)— Ic-723

—N(CH₃)— Ic-724

—N(CH₂CH₃)— Ic-725

—N(CH₂CH₂CH₃)— Ic-726

—N(CH₂CH₂CH₂CH₃)— Ic-727

—N(C(H)(CH₃)(CH₂CH₃))— Ic-728

—N(C(H)(CH₃)₂)— Ic-729

—N(CH₂C(H)(CH₃)₂)— Ic-730

—N(C(CH₃)₃)— Ic-731

—N(CH₃)— Ic-732

—N(CH₂CH₃)— Ic-733

—N(CH₂CH₂CH₃)— Ic-734

—N(CH₂CH₂CH₂CH₃)— Ic-735

—N(C(H)(CH₃)(CH₂CH₃))— Ic-736

—N(C(H)(CH₃)₂)— Ic-737

—N(CH₂C(H)(CH₃)₂)— Ic-738

—N(C(CH₃)₃)— Ic-739

—N(CH₃)— Ic-740

—N(CH₂CH₃)— Ic-741

—N(CH₂CH₂CH₃)— Ic-742

—N(CH₂CH₂CH₂CH₃)— Ic-743

—N(C(H)(CH₃)(CH₂CH₃))— Ic-744

—N(C(H)(CH₃)₂)— Ic-745

—N(CH₂C(H)(CH₃)₂)— Ic-746

—N(C(CH₃)₃)— Ic-747

—N(CH₃)— Ic-748

—N(CH₂CH₃)— Ic-749

—N(CH₂CH₂CH₃)— Ic-750

—N(CH₂CH₂CH₂CH₃)— Ic-751

—N(C(H)(CH₃)(CH₂CH₃))— Ic-752

—N(C(H)(CH₃)₂)— Ic-753

—N(CH₂C(H)(CH₃)₂)— Ic-754

—N(C(CH₃)₃)— Ic-755

—N(CH₃)— Ic-756

—N(CH₂CH₃)— Ic-757

—N(CH₂CH₂CH₃)— Ic-758

—N(CH₂CH₂CH₂CH₃)— Ic-759

—N(C(H)(CH₃)(CH₂CH₃))— Ic-760

—N(C(H)(CH₃)₂)— Ic-761

—N(CH₂C(H)(CH₃)₂)— Ic-762

—N(C(CH₃)₃)— Ic-763

—N(CH₃)— Ic-764

—N(CH₂CH₃)— Ic-765

—N(CH₂CH₂CH₃)— Ic-766

—N(CH₂CH₂CH₂CH₃)— Ic-767

—N(C(H)(CH₃)(CH₂CH₃))— Ic-768

—N(C(H)(CH₃)₂)— Ic-769

—N(CH₂C(H)(CH₃)₂)— Ic-770

—N(C(CH₃)₃)— Ic-771

—N(CH₃)— Ic-772

—N(CH₂CH₃)— Ic-773

—N(CH₂CH₂CH₃)— Ic-774

—N(CH₂CH₂CH₂CH₃)— Ic-775

—N(C(H)(CH₃)(CH₂CH₃))— Ic-776

—N(C(H)(CH₃)₂)— Ic-777

—N(CH₂C(H)(CH₃)₂)— Ic-778

—N(C(CH₃)₃)— Ic-779 —CH₂—NH—CH₃ —N(CH₃)— Ic-780 —CH₂—NH—CH₃ —N(CH₂CH₃)—Ic-781 —CH₂—NH—CH₃ —N(CH₂CH₂CH₃)— Ic-782 —CH₂—NH—CH₃ —N(CH₂CH₂CH₂CH₃)—Ic-783 —CH₂—NH—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ic-784 —CH₂—NH—CH₃—N(C(H)(CH₃)₂)— Ic-785 —CH₂—NH—CH₃ —N(CH₂C(H)(CH₃)₂)— Ic-786 —CH₂—NH—CH₃—N(C(CH₃)₃)— Ic-787 —CH₂—NH—CH₂—CH₃ —N(CH₃)— Ic-788 —CH₂—NH—CH₂—CH₃—N(CH₂CH₃)— Ic-789 —CH₂—NH—CH₂—CH₃ —N(CH₂CH₂CH₃)— Ic-790 —CH₂—NH—CH₂—CH₃—N(CH₂CH₂CH₂CH₃)— Ic-791 —CH₂—NH—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))— Ic-792—CH₂—NH—CH₂—CH₃ —N(C(H)(CH₃)₂)— Ic-793 —CH₂—NH—CH₂—CH₃—N(CH₂C(H)(CH₃)₂)— Ic-794 —CH₂—NH—CH₂—CH₃ —N(C(CH₃)₃)— Ic-795—CH₂—NH—CH₂—CH₂—CH₃ —N(CH₃)— Ic-796 —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₃)—Ic-797 —CH₂—NH—CH₂—CH₂—CH₃ —N(CH₂CH₂CH₃)— Ic-798 —CH₂—NH—CH₂—CH₂—CH₃—N(CH₂CH₂CH₂CH₃)— Ic-799 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ic-800 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(H)(CH₃)₂)— Ic-801 —CH₂—NH—CH₂—CH₂—CH₃—N(CH₂C(H)(CH₃)₂)— Ic-802 —CH₂—NH—CH₂—CH₂—CH₃ —N(C(CH₃)₃)— Ic-803

—N(CH₃)— Ic-804

—N(CH₂CH₃)— Ic-805

—N(CH₂CH₂CH₃)— Ic-806

—N(CH₂CH₂CH₂CH₃)— Ic-807

—N(C(H)(CH₃)(CH₂CH₃))— Ic-808

—N(C(H)(CH₃)₂)— Ic-809

—N(CH₂C(H)(CH₃)₂)— Ic-810

—N(C(CH₃)₃)— Ic-811

—N(CH₃)— Ic-812

—N(CH₂CH₃)— Ic-813

—N(CH₂CH₂CH₃)— Ic-814

—N(CH₂CH₂CH₂CH₃)— Ic-815

—N(C(H)(CH₃)(CH₂CH₃))— Ic-816

—N(C(H)(CH₃)₂)— Ic-817

—N(CH₂C(H)(CH₃)₂)— Ic-818

—N(C(CH₃)₃)— Ic-819

—N(CH₃)— Ic-820

—N(CH₂CH₃)— Ic-821

—N(CH₂CH₂CH₃)— Ic-822

—N(CH₂CH₂CH₂CH₃)— Ic-823

—N(C(H)(CH₃)(CH₂CH₃))— Ic-824

—N(C(H)(CH₃)₂)— Ic-825

—N(CH₂C(H)(CH₃)₂)— Ic-826

—N(C(CH₃)₃)— Ic-827

—N(CH₃)— Ic-828

—N(CH₂CH₃)— Ic-829

—N(CH₂CH₂CH₃)— Ic-830

—N(CH₂CH₂CH₂CH₃)— Ic-831

—N(C(H)(CH₃)(CH₂CH₃))— Ic-832

—N(C(H)(CH₃)₂)— Ic-833

—N(CH₂C(H)(CH₃)₂)— Ic-834

—N(C(CH₃)₃)— Ic-835

—N(CH₃)— Ic-836

—N(CH₂CH₃)— Ic-837

—N(CH₂CH₂CH₃)— Ic-838

—N(CH₂CH₂CH₂CH₃)— Ic-839

—N(C(H)(CH₃)(CH₂CH₃))— Ic-840

—N(C(H)(CH₃)₂)— Ic-841

—N(CH₂C(H)(CH₃)₂)— Ic-842

—N(C(CH₃)₃)— Ic-843

—N(CH₃)— Ic-844

—N(CH₂CH₃)— Ic-845

—N(CH₂CH₂CH₃)— Ic-846

—N(CH₂CH₂CH₂CH₃)— Ic-847

—N(C(H)(CH₃)(CH₂CH₃))— Ic-848

—N(C(H)(CH₃)₂)— Ic-849

—N(CH₂C(H)(CH₃)₂)— Ic-850

—N(C(CH₃)₃)— Ic-851

—N(CH₃)— Ic-852

—N(CH₂CH₃)— Ic-853

—N(CH₂CH₂CH₃)— Ic-854

—N(CH₂CH₂CH₂CH₃)— Ic-855

—N(C(H)(CH₃)(CH₂CH₃))— Ic-856

—N(C(H)(CH₃)₂)— Ic-857

—N(CH₂C(H)(CH₃)₂)— Ic-858

—N(C(CH₃)₃)— Ic-859

—N(CH₃)— Ic-860

—N(CH₂CH₃)— Ic-861

—N(CH₂CH₂CH₃)— Ic-862

—N(CH₂CH₂CH₂CH₃)— Ic-863

—N(C(H)(CH₃)(CH₂CH₃))— Ic-864

—N(C(H)(CH₃)₂)— Ic-865

—N(CH₂C(H)(CH₃)₂)— Ic-866

—N(C(CH₃)₃)— Ic-867

—N(CH₃)— Ic-868

—N(CH₂CH₃)— Ic-869

—N(CH₂CH₂CH₃)— Ic-870

—N(CH₂CH₂CH₂CH₃)— Ic-871

—N(C(H)(CH₃)(CH₂CH₃))— Ic-872

—N(C(H)(CH₃)₂)— Ic-873

—N(CH₂C(H)(CH₃)₂)— Ic-874

—N(C(CH₃)₃)— Ic-875

—N(CH₃)— Ic-876

—N(CH₂CH₃)— Ic-877

—N(CH₂CH₂CH₃)— Ic-878

—N(CH₂CH₂CH₂CH₃)— Ic-879

—N(C(H)(CH₃)(CH₂CH₃))— Ic-880

—N(C(H)(CH₃)₂)— Ic-881

—N(CH₂C(H)(CH₃)₂)— Ic-882

—N(C(CH₃)₃)— Ic-883

—N(CH₃)— Ic-884

—N(CH₂CH₃)— Ic-885

—N(CH₂CH₂CH₃)— Ic-886

—N(CH₂CH₂CH₂CH₃)— Ic-887

—N(C(H)(CH₃)(CH₂CH₃))— Ic-888

—N(C(H)(CH₃)₂)— Ic-889

—N(CH₂C(H)(CH₃)₂)— Ic-890

—N(C(CH₃)₃)— Ic-891

—N(CH₃)— Ic-892

—N(CH₂CH₃)— Ic-893

—N(CH₂CH₂CH₃)— Ic-894

—N(CH₂CH₂CH₂CH₃)— Ic-895

—N(C(H)(CH₃)(CH₂CH₃))— Ic-896

—N(C(H)(CH₃)₂)— Ic-897

—N(CH₂C(H)(CH₃)₂)— Ic-898

—N(C(CH₃)₃)— Ic-899

—N(CH₃)— Ic-900

—N(CH₂CH₃)— Ic-901

—N(CH₂CH₂CH₃)— Ic-902

—N(CH₂CH₂CH₂CH₃)— Ic-903

—N(C(H)(CH₃)(CH₂CH₃))— Ic-904

—N(C(H)(CH₃)₂)— Ic-905

—N(CH₂C(H)(CH₃)₂)— Ic-906

—N(C(CH₃)₃)— Ic-907

—N(CH₃)— Ic-908

—N(CH₂CH₃)— Ic-909

—N(CH₂CH₂CH₃)— Ic-910

—N(CH₂CH₂CH₂CH₃)— Ic-911

—N(C(H)(CH₃)(CH₂CH₃))— Ic-912

—N(C(H)(CH₃)₂)— Ic-913

—N(CH₂C(H)(CH₃)₂)— Ic-914

—N(C(CH₃)₃)— Ic-915

—N(CH₃)— Ic-916

—N(CH₂CH₃)— Ic-917

—N(CH₂CH₂CH₃)— Ic-918

—N(CH₂CH₂CH₂CH₃)— Ic-919

—N(C(H)(CH₃)(CH₂CH₃))— Ic-920

—N(C(H)(CH₃)₂)— Ic-921

—N(CH₂C(H)(CH₃)₂)— Ic-922

—N(C(CH₃)₃)— Ic-923

—N(CH₃)— Ic-924

—N(CH₂CH₃)— Ic-925

—N(CH₂CH₂CH₃)— Ic-926

—N(CH₂CH₂CH₂CH₃)— Ic-927

—N(C(H)(CH₃)(CH₂CH₃))— Ic-928

—N(C(H)(CH₃)₂)— Ic-929

—N(CH₂C(H)(CH₃)₂)— Ic-930

—N(C(CH₃)₃)— Ic-931

—N(CH₃)— Ic-932

—N(CH₂CH₃)— Ic-933

—N(CH₂CH₂CH₃)— Ic-934

—N(CH₂CH₂CH₂CH₃)— Ic-935

—N(C(H)(CH₃)(CH₂CH₃))— Ic-936

—N(C(H)(CH₃)₂)— Ic-937

—N(CH₂C(H)(CH₃)₂)— Ic-938

—N(C(CH₃)₃)— Ic-939

—N(CH₃)— Ic-940

—N(CH₂CH₃)— Ic-941

—N(CH₂CH₂CH₃)— Ic-942

—N(CH₂CH₂CH₂CH₃)— Ic-943

—N(C(H)(CH₃)(CH₂CH₃))— Ic-944

—N(C(H)(CH₃)₂)— Ic-945

—N(CH₂C(H)(CH₃)₂)— Ic-946

—N(C(CH₃)₃)— Ic-947

—N(CH₃)— Ic-948

—N(CH₂CH₃)— Ic-949

—N(CH₂CH₂CH₃)— Ic-950

—N(CH₂CH₂CH₂CH₃)— Ic-951

—N(C(H)(CH₃)(CH₂CH₃))— Ic-952

—N(C(H)(CH₃)₂)— Ic-953

—N(CH₂C(H)(CH₃)₂)— Ic-954

—N(C(CH₃)₃)— Ic-955

—N(CH₃)— Ic-956

—N(CH₂CH₃)— Ic-957

—N(CH₂CH₂CH₃)— Ic-958

—N(CH₂CH₂CH₂CH₃)— Ic-959

—N(C(H)(CH₃)(CH₂CH₃))— Ic-960

—N(C(H)(CH₃)₂)— Ic-961

—N(CH₂C(H)(CH₃)₂)— Ic-962

—N(C(CH₃)₃)— Ic-963 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₃)— Ic-964—CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ic-965 —CH₂—N(CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ic-966 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ic-967—CH₂—N(CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ic-968 —CH₂—N(CH₂CH₃)(CH₃)—N(C(H)(CH₃)₂)— Ic-969 —CH₂—N(CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ic-970—CH₂—N(CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ic-971 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₃)—Ic-972 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₃)— Ic-973 —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(CH₂CH₂CH₃)— Ic-974 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ic-975—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ic-976—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ic-977 —CH₂—N(CH₂CH₂CH₃)(CH₃)—N(CH₂C(H)(CH₃)₂)— Ic-978 —CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ic-979—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₃)— Ic-980 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(CH₂CH₃)— Ic-981 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₃)— Ic-982—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂CH₂CH₂CH₃)— Ic-983—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)(CH₂CH₃))— Ic-984—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(H)(CH₃)₂)— Ic-985—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(CH₂C(H)(CH₃)₂)— Ic-986—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —N(C(CH₃)₃)— Ic-987 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₃)— Ic-988 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₃)— Ic-989—CH₂—NH—CH₂CH₂CH₂CH₃ —N(CH₂CH₂CH₃)— Ic-990 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₂CH₂CH₂CH₃)— Ic-991 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ic-992 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(H)(CH₃)₂)— Ic-993 —CH₂—NH—CH₂CH₂CH₂CH₃—N(CH₂C(H)(CH₃)₂)— Ic-994 —CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(CH₃)₃)— Ic-995—CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₃)— Ic-996 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₃)—Ic-997 —CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂CH₂CH₃)— Ic-998 —CH₂—NH—CH₂CH₂—O—CH₃—N(CH₂CH₂CH₂CH₃)— Ic-999 —CH₂—NH—CH₂CH₂—O—CH₃ —N(C(H)(CH₃)(CH₂CH₃))—Ic-1000 —CH₂—NH—CH₂CH₂—O—CH₃ —N(C(H)(CH₃)₂)— Ic-1001—CH₂—NH—CH₂CH₂—O—CH₃ —N(CH₂C(H)(CH₃)₂)— Ic-1002 —CH₂—NH—CH₂CH₂—O—CH₃—N(C(CH₃)₃)— Ic-1003

—N(CH₃)— Ic-1004

—N(CH₂CH₃)— Ic-1005

—N(CH₂CH₂CH₃)— Ic-1006

—N(CH₂CH₂CH₂CH₃)— Ic-1007

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1008

—N(C(H)(CH₃)₂)— Ic-1009

—N(CH₂C(H)(CH₃)₂)— Ic-1010

—N(C(CH₃)₃)— Ic-1011

—N(CH₃)— Ic-1012

—N(CH₂CH₃)— Ic-1013

—N(CH₂CH₂CH₃)— Ic-1014

—N(CH₂CH₂CH₂CH₃)— Ic-1015

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1016

—N(C(H)(CH₃)₂)— Ic-1017

—N(CH₂C(H)(CH₃)₂)— Ic-1018

—N(C(CH₃)₃)— Ic-1019

—N(CH₃)— Ic-1020

—N(CH₂CH₃)— Ic-1021

—N(CH₂CH₂CH₃)— Ic-1022

—N(CH₂CH₂CH₂CH₃)— Ic-1023

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1024

—N(C(H)(CH₃)₂)— Ic-1025

—N(CH₂C(H)(CH₃)₂)— Ic-1026

—N(C(CH₃)₃)— Ic-1027

—N(CH₃)— Ic-1028

—N(CH₂CH₃)— Ic-1029

—N(CH₂CH₂CH₃)— Ic-1030

—N(CH₂CH₂CH₂CH₃)— Ic-1031

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1032

—N(C(H)(CH₃)₂)— Ic-1033

—N(CH₂C(H)(CH₃)₂)— Ic-1034

—N(C(CH₃)₃)— Ic-1035

—N(CH₃)— Ic-1036

—N(CH₂CH₃)— Ic-1037

—N(CH₂CH₂CH₃)— Ic-1038

—N(CH₂CH₂CH₂CH₃)— Ic-1039

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1040

—N(C(H)(CH₃)₂)— Ic-1041

—N(CH₂C(H)(CH₃)₂)— Ic-1042

—N(C(CH₃)₃)— Ic-1043

—N(CH₃)— Ic-1044

—N(CH₂CH₃)— Ic-1045

—N(CH₂CH₂CH₃)— Ic-1046

—N(CH₂CH₂CH₂CH₃)— Ic-1047

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1048

—N(C(H)(CH₃)₂)— Ic-1049

—N(CH₂C(H)(CH₃)₂)— Ic-1050

—N(C(CH₃)₃)— Ic-1051

—N(CH₃)— Ic-1052

—N(CH₂CH₃)— Ic-1053

—N(CH₂CH₂CH₃)— Ic-1054

—N(CH₂CH₂CH₂CH₃)— Ic-1055

—N(C(H)(CH₃)(CH₂CH₃))— Ic-1056

—N(C(H)(CH₃)₂)— Ic-1057

—N(CH₂C(H)(CH₃)₂)— Ic-1058

—N(C(CH₃)₃)— Compound n —R¹ X Ic-c1 1 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c22 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c3 3 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c44 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c5 5 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c66 —(CH₂)_(n)—N(CH₃)₂ —CH(OH)— Ic-c7 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c8 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c9 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c10 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c11 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c12 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c13 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c14 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c15 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c16 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c17 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c18 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c19 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c20 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c21 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c22 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c23 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c24 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c25 1 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c26 2 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c27 3 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c28 4 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c29 5 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c30 6 —(CH₂)_(n)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c31 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ic-c32 2 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c33 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ic-c34 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c35 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c36 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ic-c37 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c38 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c39 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ic-c40 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c41 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c42 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—F)— Ic-c43 1 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c44 2—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c45 3 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ic-c46 4 —(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c47 5—(CH₂)_(n)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c48 6 —(CH₂)_(n)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ic-c49 1

—CH(OH)— Ic-c50 2

—CH(OH)— Ic-c51 3

—CH(OH)— Ic-c52 4

—CH(OH)— Ic-c53 5

—CH(OH)— Ic-c54 6

—CH(OH)— Ic-c55 1

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c56 2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c57 3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c58 4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c59 5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c60 6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c61 1

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c62 2

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c63 3

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c64 4

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c65 5

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c66 6

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c67 1

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c68 2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c69 3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c70 4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c71 5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c72 6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c73 1

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c74 2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c75 3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c76 4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c77 5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c78 6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c79 1

—N(CH₂—CH₂—OH)— Ic-c80 2

—N(CH₂—CH₂—OH)— Ic-c81 3

—N(CH₂—CH₂—OH)— Ic-c82 4

—N(CH₂—CH₂—OH)— Ic-c83 5

—N(CH₂—CH₂—OH)— Ic-c84 6

—N(CH₂—CH₂—OH)— Ic-c85 1

—N(CH₂—CH₂—F)— Ic-c86 2

—N(CH₂—CH₂—F)— Ic-c87 3

—N(CH₂—CH₂—F)— Ic-c88 4

—N(CH₂—CH₂—F)— Ic-c89 5

—N(CH₂—CH₂—F)— Ic-c90 6

—N(CH₂—CH₂—F)— Ic-c91 1

—N(CH₂—CH₂—OCH₃)— Ic-c92 2

—N(CH₂—CH₂—OCH₃)— Ic-c93 3

—N(CH₂—CH₂—OCH₃)— Ic-c94 4

—N(CH₂—CH₂—OCH₃)— Ic-c95 5

—N(CH₂—CH₂—OCH₃)— Ic-c96 6

—N(CH₂—CH₂—OCH₃)— Compound m —R¹ X Ic-c146 2 —O—(CH₂)_(m)—N(CH₃)₂—CH(OH)— Ic-c147 3 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ic-c148 4—O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ic-c149 5 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)—Ic-c150 6 —O—(CH₂)_(m)—N(CH₃)₂ —CH(OH)— Ic-c151 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c152 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c153 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c154 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c155 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c156 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c157 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c158 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c159 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c160 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c161 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c162 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c163 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c164 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c165 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c166 2 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c167 3 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c168 4 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c169 5 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c170 6 —O—(CH₂)_(m)—N(CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c171 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)—Ic-c172 3 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c173 4—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c174 5 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OH)— Ic-c175 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OH)— Ic-c176 2—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c178 3 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ic-c179 4 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c180 5—O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—F)— Ic-c181 6 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—F)— Ic-c182 2 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c1833 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c184 4 —O—(CH₂)_(m)—N(CH₃)₂—N(CH₂—CH₂—OCH₃)— Ic-c185 5 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)—Ic-c186 6 —O—(CH₂)_(m)—N(CH₃)₂ —N(CH₂—CH₂—OCH₃)— Ic-c187 2

—CH(OH)— Ic-c188 3

—CH(OH)— Ic-c189 4

—CH(OH)— Ic-c190 5

—CH(OH)— Ic-c191 6

—CH(OH)— Ic-c192 2

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c193 3

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c194 4

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c195 5

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c196 6

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c197 2

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c198 3

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c199 4

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c200 5

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c201 6

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c202 2

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c203 3

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c204 4

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c205 5

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c206 6

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c207 2

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c208 3

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c209 4

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c210 5

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c211 6

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c212 2

—N(CH₂—CH₂—OH)— Ic-c213 3

—N(CH₂—CH₂—OH)— Ic-c214 4

—N(CH₂—CH₂—OH)— Ic-c215 5

—N(CH₂—CH₂—OH)— Ic-c216 6

—N(CH₂—CH₂—OH)— Ic-c217 2

—N(CH₂—CH₂—F)— Ic-c218 3

—N(CH₂—CH₂—F)— Ic-c219 4

—N(CH₂—CH₂—F)— Ic-c220 5

—N(CH₂—CH₂—F)— Ic-c221 6

—N(CH₂—CH₂—F)— Ic-c222 2

—N(CH₂—CH₂—OCH₃)— Ic-c223 3

—N(CH₂—CH₂—OCH₃)— Ic-c224 4

—N(CH₂—CH₂—OCH₃)— Ic-c225 5

—N(CH₂—CH₂—OCH₃)— Ic-c226 6

—N(CH₂—CH₂—OCH₃)— Compound —R¹ X Ic-c267 —CH₂—N(CH₂—CH₃)₂ —CH(OH)—Ic-c268 —CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c269—CH₂—N(CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c270 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c271 —CH₂—N(CH₂—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c275 —CH₂—N(CH₂—CH₂—CH₃)₂ —CH(OH)— Ic-c276—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c277—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c278—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c279—CH₂—N(CH₂—CH₂—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c283—CH₂—N(CH₂—CH₂OH)₂ —CH(OH)— Ic-c284 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c285 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c286 —CH₂—N(CH₂—CH₂OH)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c291 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)—Ic-c292 —CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c293—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c294—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c295—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c296—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c297—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ic-c298—CH₂—N(CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c299—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —CH(OH)— Ic-c300—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c301—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c302—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c303—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c304—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c305—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ —N(C(O)N(H)—CH₂—CF₃)— Ic-c306—CH₂—N(CH₂—CH₂—CH₂—N(CH₃)₂)₂ N(C(O)N(H)—(CH₂)₃—OH)— Ic-c307

—CH(OH)— Ic-c308

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c309

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c310

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c311

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c312

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c313

—N(C(O)N(H)—CH₂—CF₃)— Ic-c314

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c315

—CH(OH)— Ic-c316

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c317

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c318

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c319

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c320

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c321

—N(C(O)N(H)—CH₂—CF₃)— Ic-c322

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c323

—CH(OH)— Ic-c324

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c325

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c326

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c327

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c328

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c329

—N(C(O)N(H)—CH₂—CF₃)— Ic-c330

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c331

—CH(OH)— Ic-c332

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c333

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c334

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c335

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c336

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c337

—N(C(O)N(H)—CH₂—CF₃)— Ic-c338

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c339

—CH(OH)— Ic-c340

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c341

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c342

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c343

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c344

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c345

—N(C(O)N(H)—CH₂—CF₃)— Ic-c346

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c347

—CH(OH)— Ic-c348

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c349

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c350

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c351

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c352

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c353

—N(C(O)N(H)—CH₂—CF₃)— Ic-c354

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c355

—CH(OH)— Ic-c356

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c357

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c358

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c359

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c360

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c361

—N(C(O)N(H)—CH₂—CF₃)— Ic-c362

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c363

—CH(OH)— Ic-c364

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c365

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c366

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c367

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c368

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c369

—N(C(O)N(H)—CH₂—CF₃)— Ic-c370

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c371

—CH(OH)— Ic-c372

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c373

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c374

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c375

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c376

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c377

—N(C(O)N(H)—CH₂—CF₃)— Ic-c378

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c379

—CH(OH)— Ic-c380

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c381

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c382

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c383

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c384

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c385

—N(C(O)N(H)—CH₂—CF₃)— Ic-c386

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c387

—CH(OH)— Ic-c388

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c389

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c390

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c391

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c392

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c393

—N(C(O)N(H)—CH₂—CF₃)— Ic-c394

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c395

—CH(OH)— Ic-c396

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c397

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c398

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c399

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c400

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c401

—N(C(O)N(H)—CH₂—CF₃)— Ic-c402

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c403

—CH(OH)— Ic-c404

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c405

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c406

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c407

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c408

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c409

—N(C(O)N(H)—CH₂—CF₃)— Ic-c410

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c411

—CH(OH)— Ic-c412

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c413

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c414

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c415

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c416

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c417

—N(C(O)N(H)—CH₂—CF₃)— Ic-c418

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c419

—CH(OH)— Ic-c420

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c421

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c422

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c423

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c424

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c425

—N(C(O)N(H)—CH₂—CF₃)— Ic-c426

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c427

—CH(OH)— Ic-c428

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c429

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c430

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c431

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c432

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c433

—N(C(O)N(H)—CH₂—CF₃)— Ic-c434

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c435

—CH(OH)— Ic-c436

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c437

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c438

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c439

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c440

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c441

—N(C(O)N(H)—CH₂—CF₃)— Ic-c442

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c443

—CH(OH)— Ic-c444

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c445

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c446

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c447

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c448

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c449

—N(C(O)N(H)—CH₂—CF₃)— Ic-c450

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c451

—CH(OH)— Ic-c452

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c453

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c454

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c455

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c456

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c457

—N(C(O)N(H)—CH₂—CF₃)— Ic-c458

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c459

—CH(OH)— Ic-c460

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c461

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c462

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c463

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c464

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c465

—N(C(O)N(H)—CH₂—CF₃)— Ic-c466

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c467

—CH(OH)— Ic-c468

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c469

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c470

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c471

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c472

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c473

—N(C(O)N(H)—CH₂—CF₃)— Ic-c474

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c475

—CH(OH)— Ic-c476

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c477

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c478

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c479

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c480

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c481

N(C(O)N(H)—CH₂—CF₃)— Ic-c482

N(C(O)N(H)—(CH₂)₃—OH)— Ic-c483

—CH(OH)— Ic-c484

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c485

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c486

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c487

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c488

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c489

N(C(O)N(H)—CH₂—CF₃)— Ic-c490

N(C(O)N(H)—(CH₂)₃—OH)— Ic-c491 —CH₂—CH₂—CH₂—OP(O)(OH)₂ —CH(OH)— Ic-c492—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c493—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c494—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c495—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c496—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c497—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—CH₂—CF₃)— Ic-c498—CH₂—CH₂—CH₂—OP(O)(OH)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c499—CH₂—CH₂—CH₂—OS(O)₂OH —CH(OH)— Ic-c500 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c501 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c502 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c503 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c504 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c505 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—CH₂—CF₃)— Ic-c506 —CH₂—CH₂—CH₂—OS(O)₂OH—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c507

—CH(OH)— Ic-c508

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c509

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c510

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c511

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c512

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c513

—N(C(O)N(H)—CH₂—CF₃)— Ic-c514

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c515

—CH(OH)— Ic-c516

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c517

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c518

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c519

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c520

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c521

—N(C(O)N(H)—CH₂—CF₃)— Ic-c522

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c523 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)—Ic-c524 —(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c525—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c526—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c527—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c528—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c529—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ic-c530—(CH₂)₁₀—N(CH₂—CH₂—O—CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c531—CH₂—N(CH₂—CH₂—O—CH₃)₂ —CH(OH)— Ic-c532 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c533 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c534 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c535 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c536 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c537 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—CH₂—CF₃)— Ic-c538 —CH₂—N(CH₂—CH₂—O—CH₃)₂—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c539

—CH(OH)— Ic-c540

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c541

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c542

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c543

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c544

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c545

—N(C(O)N(H)—CH₂—CF₃)— Ic-c546

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c547

—CH(OH)— Ic-c548

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c549

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c550

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c551

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c552

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c553

—N(C(O)N(H)—CH₂—CF₃)— Ic-c554

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c555

—CH(OH)— Ic-c556

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c557

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c558

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c559

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c560

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c561

—N(C(O)N(H)—CH₂—CF₃)— Ic-c562

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c563

—CH(OH)— Ic-c564

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c565

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c566

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c567

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c568

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c569

—N(C(O)N(H)—CH₂—CF₃)— Ic-c570

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c571

—CH(OH)— Ic-c572

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c573

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c574

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c575

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c576

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c577

—N(C(O)N(H)—CH₂—CF₃)— Ic-c578

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c579

—CH(OH)— Ic-c580

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c581

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c582

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c583

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c584

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c585

—N(C(O)N(H)—CH₂—CF₃)— Ic-c586

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c587

—CH(OH)— Ic-c588

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c589

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c590

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c591

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c592

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c593

—N(C(O)N(H)—CH₂—CF₃)— Ic-c594

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c595

—CH(OH)— Ic-c596

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c597

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c598

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c599

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c600

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c601

—N(C(O)N(H)—CH₂—CF₃)— Ic-c602

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c603

—CH(OH)— Ic-c604

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c605

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c606

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c607

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c608

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c609

—N(C(O)N(H)—CH₂—CF₃)— Ic-c610

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c611 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —CH(OH)—Ic-c612 —CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c613—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c614—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c615—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c616—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c617—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—CH₂—CF₃)— Ic-c618—CH₂—NH—CH₂—CH₂—CH₂—N(CH₃)₂ —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c619

—CH(OH)— Ic-c620

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c621

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c622

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c623

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c624

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c625

—N(C(O)N(H)—CH₂—CF₃)— Ic-c626

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c627

—CH(OH)— Ic-c628

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c629

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c630

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c631

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c632

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c633

—N(C(O)N(H)—CH₂—CF₃)— Ic-c634

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c635

—CH(OH)— Ic-c636

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c637

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c638

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c639

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c640

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c641

—N(C(O)N(H)—CH₂—CF₃)— Ic-c642

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c643

—CH(OH)— Ic-c644

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c645

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c646

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c647

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c648

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c649

—N(C(O)N(H)—CH₂—CF₃)— Ic-c650

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c651

—CH(OH)— Ic-c652

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c653

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c654

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c655

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c656

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c657

—N(C(O)N(H)—CH₂—CF₃)— Ic-c658

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c659

—CH(OH)— Ic-c660

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c661

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c662

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c663

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c664

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c665

—N(C(O)N(H)—CH₂—CF₃)— Ic-c666

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c667

—CH(OH)— Ic-c668

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c669

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c670

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c671

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c672

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c673

—N(C(O)N(H)—CH₂—CF₃)— Ic-c674

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c675

—CH(OH)— Ic-c676

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c677

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c678

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c679

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c680

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c681

—N(C(O)N(H)—CH₂—CF₃)— Ic-c682

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c683

—CH(OH)— Ic-c684

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c685

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c686

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c687

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c688

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c689

—N(C(O)N(H)—CH₂—CF₃)— Ic-c690

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c691

—CH(OH)— Ic-c692

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c693

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c694

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c695

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c696

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c697

—N(C(O)N(H)—CH₂—CF₃)— Ic-c698

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c699

—CH(OH)— Ic-c700

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c701

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c702

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c703

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c704

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c705

—N(C(O)N(H)—CH₂—CF₃)— Ic-c706

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c707

—CH(OH)— Ic-c708

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c709

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c710

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c711

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c712

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c713

—N(C(O)N(H)—CH₂—CF₃)— Ic-c714

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c715

—CH(OH)— Ic-c716

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c717

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c718

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c719

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c720

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c721

—N(C(O)N(H)—CH₂—CF₃)— Ic-c722

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c723

—CH(OH)— Ic-c724

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c725

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c726

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c727

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c728

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c729

—N(C(O)N(H)—CH₂—CF₃)— Ic-c730

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c731

—CH(OH)— Ic-c732

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c733

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c734

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c735

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c736

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c737

—N(C(O)N(H)—CH₂—CF₃)— Ic-c738

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c739

—CH(OH)— Ic-c740

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c741

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c742

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c743

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c744

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c745

—N(C(O)N(H)—CH₂—CF₃)— Ic-c746

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c747

—CH(OH)— Ic-c748

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c749

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c750

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c751

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c752

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c753

—N(C(O)N(H)—CH₂—CF₃)— Ic-c754

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c755

—CH(OH)— Ic-c756

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c757

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c758

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c759

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c760

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c761

—N(C(O)N(H)—CH₂—CF₃)— Ic-c762

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c763

—CH(OH)— Ic-c764

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c765

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c766

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c767

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c768

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c769

—N(C(O)N(H)—CH₂—CF₃)— Ic-c770

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c771

—CH(OH)— Ic-c772

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c773

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c774

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c775

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c776

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c777

—N(C(O)N(H)—CH₂—CF₃)— Ic-c778

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c779 —CH₂—NH—CH₃ —CH(OH)— Ic-c780 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c781 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)—Ic-c782 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c783 —CH₂—NH—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c784 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)—Ic-c785 —CH₂—NH—CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ic-c786 —CH₂—NH—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c787 —CH₂—NH—CH₂—CH₃ —CH(OH)— Ic-c788—CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c789 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c790 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c791 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c792 —CH₂—NH—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c793 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—CH₂—CF₃)—Ic-c794 —CH₂—NH—CH₂—CH₃ —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c795—CH₂—NH—CH₂—CH₂—CH₃ —CH(OH)— Ic-c796 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c797 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c798 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c799 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c800 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c801 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—CH₂—CF₃)— Ic-c802 —CH₂—NH—CH₂—CH₂—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c803

—CH(OH)— Ic-c804

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c805

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c806

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c807

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c808

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c809

—N(C(O)N(H)—CH₂—CF₃)— Ic-c810

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c811

—CH(OH)— Ic-c812

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c813

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c814

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c815

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c816

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c817

N(C(O)N(H)—CH₂—CF₃)— Ic-c818

N(C(O)N(H)—(CH₂)₃—OH)— Ic-c819

—CH(OH)— Ic-c820

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c821

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c822

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c823

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c824

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c825

—N(C(O)N(H)—CH₂—CF₃)— Ic-c826

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c827

—CH(OH)— Ic-c828

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c829

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c830

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c831

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c832

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c833

—N(C(O)N(H)—CH₂—CF₃)— Ic-c834

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c835

—CH(OH)— Ic-c836

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c837

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c838

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c839

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c840

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c841

—N(C(O)N(H)—CH₂—CF₃)— Ic-c842

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c843

—CH(OH)— Ic-c844

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c845

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c846

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c847

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c848

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c849

—N(C(O)N(H)—CH₂—CF₃)— Ic-c850

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c851

—CH(OH)— Ic-c852

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c853

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c854

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c855

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c856

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c857

—N(C(O)N(H)—CH₂—CF₃)— Ic-c858

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c859

—CH(OH)— Ic-c860

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c861

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c862

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c863

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c864

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c865

—N(C(O)N(H)—CH₂—CF₃)— Ic-c866

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c867

—CH(OH)— Ic-c868

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c869

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c870

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c871

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c872

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c873

—N(C(O)N(H)—CH₂—CF₃)— Ic-c874

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c875

—CH(OH)— Ic-c876

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c877

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c878

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c879

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c880

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c881

—N(C(O)N(H)—CH₂—CF₃)— Ic-c882

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c883

—CH(OH)— Ic-c884

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c885

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c886

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c887

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c888

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c889

—N(C(O)N(H)—CH₂—CF₃)— Ic-c890

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c891

—CH(OH)— Ic-c892

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c893

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c894

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c895

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c896

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c897

—N(C(O)N(H)—CH₂—CF₃)— Ic-c898

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c899

—CH(OH)— Ic-c900

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c901

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c902

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c903

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c904

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c905

—N(C(O)N(H)—CH₂—CF₃)— Ic-c906

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c907

—CH(OH)— Ic-c908

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c909

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c910

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c911

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c912

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c913

—N(C(O)N(H)—CH₂—CF₃)— Ic-c914

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c915

—CH(OH)— Ic-c916

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c917

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c918

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c919

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c920

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c921

—N(C(O)N(H)—CH₂—CF₃)— Ic-c922

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c923

—CH(OH)— Ic-c924

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c925

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c926

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c927

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c928

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c929

—N(C(O)N(H)—CH₂—CF₃)— Ic-c930

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c931

—CH(OH)— Ic-c932

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c933

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c934

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c935

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c936

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c937

—N(C(O)N(H)—CH₂—CF₃)— Ic-c938

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c939

—CH(OH)— Ic-c940

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c941

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c942

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c943

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c944

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c945

—N(C(O)N(H)—CH₂—CF₃)— Ic-c946

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c947

—CH(OH)— Ic-c948

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c949

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c950

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c951

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c952

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c953

—N(C(O)N(H)—CH₂—CF₃)— Ic-c954

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c955

—CH(OH)— Ic-c956

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c957

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c958

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c959

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c960

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c961

—N(C(O)N(H)—CH₂—CF₃)— Ic-c962

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c963 —CH₂—N(CH₂CH₃)(CH₃) —CH(OH)— Ic-c964—CH₂—N(CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c965 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c966 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c967 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c968 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c969 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ic-c970 —CH₂—N(CH₂CH₃)(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c971 —CH₂—N(CH₂CH₂CH₃)(CH₃) —CH(OH)— Ic-c972—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c973—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c974—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c975—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c976—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c977—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—CH₂—CF₃)— Ic-c978—CH₂—N(CH₂CH₂CH₃)(CH₃) —N(C(O)N(H)—(CH₂)₃—OH)— Ic-c979—CH₂—N(CH₂CH₂CH₂CH₃)(CH₃) —CH(OH)— Ic-c980 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c981 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c982 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c983 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c984 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c985 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—CH₂—CF₃)— Ic-c986 —CH₂—N(CH₂CH₂CH₂CH₃)(CH₃)—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c987 —CH₂—NH—CH₂CH₂CH₂CH₃ —CH(OH)— Ic-c988—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c989—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c990—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c991—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c992—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c993—CH₂—NH—CH₂CH₂CH₂CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ic-c994 —CH₂—NH—CH₂CH₂CH₂CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c995 —CH₂—NH—CH₂CH₂—O—CH₃ —CH(OH)— Ic-c996—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c997—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—F)— Ic-c998—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c999—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1000—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1001—CH₂—NH—CH₂CH₂—O—CH₃ —N(C(O)N(H)—CH₂—CF₃)— Ic-c1002 —CH₂—NH—CH₂CH₂—O—CH₃—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1003

—CH(OH)— Ic-c1004

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1005

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1006

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1007

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1008

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1009

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1010

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1011

—CH(OH)— Ic-c1012

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1013

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1014

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1015

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1016

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1017

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1018

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1019

—CH(OH)— Ic-c1020

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1021

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1022

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1023

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1024

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1025

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1026

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1027

—CH(OH)— Ic-c1028

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1029

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1030

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1031

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1032

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1033

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1034

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1035

—CH(OH)— Ic-c1036

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1037

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1038

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1039

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1040

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1041

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1042

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1043

—CH(OH)— Ic-c1044

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1045

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1046

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1047

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1048

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1049

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1050

—N(C(O)N(H)—(CH₂)₃—OH)— Ic-c1051

—CH(OH)— Ic-c1052

—N(C(O)N(H)—CH₂—CH₂—OH)— Ic-c1053

—N(C(O)N(H)—CH₂—CH₂—F)— Ic-c1054

—N(C(O)N(H)—CH₂—CH₂—OCH₃)— Ic-c1055

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1056

—N(C(O)N(H)—CH₂—CH₂—CF₃)— Ic-c1057

—N(C(O)N(H)—CH₂—CF₃)— Ic-c1058

—N(C(O)N(H)—(CH₂)₃—OH)—

and pharmaceutically acceptable salts thereof.

5.5 The Indenoisoquinolinone Analogs of Formula (IIa)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IIa), below:

and pharmaceutically acceptable salts thereof,wherein:

X and R¹ are as defined above for the compounds of Formula (Ia).

In one embodiment, X is —CH₂—. In another embodiment, X is —O—. Inanother embodiment, X is —C(O)—. In another embodiment, X is —NH—. Inanother embodiment, X is —N(C₁-C₄ alkyl)-. In another embodiment, X is—S—. In another embodiment, X is —CH(OH)—.

In one embodiment, n is 1. In another embodiment, n is 2.

In one embodiment, X is —CH₂— and n is 1.

In one embodiment, X is —CH₂— and n is 2.

In one embodiment, X is —CH(OH)— and n is 1.

In one embodiment, X is —CH(OH)— and n is 2.

In one embodiment, R² is —C₁-C₆ alkyl and R³ is —C(O)—(C₁-C₆alkylene)-(3- to 7-membered monocyclic heterocycle).

In one embodiment, R² is —H and R³ is —C(O)—(C₁-C₆ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, n is 1 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 1 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, n is 2 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 2 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, n is 1 and N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, X is —CH₂—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH₂—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is a nitrogen-containing3- to 7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH₂—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH(OH)—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In various embodiments, —R¹ is:

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IIa) in which n is 1 as set forth below:

(IIa)

Compound —R¹ X IIa-1

—CH₂— IIa-a1

—CH(OH)— IIa-2

—O— IIa-3

—C(O)— IIa-4

—NH— IIa-5

—S— IIa-6

—N(CH₃)— IIa-7

—N(CH₂CH₃)— IIa-8

—N(CH₂CH₂CH₃)— IIa-9

—N(CH₂CH₂CH₂CH₃)— IIa-10

—N(C(H)(CH₃)(CH₂CH₃))— IIa-11

—N(C(H)(CH₃)₂)— IIa-12

—N(CH₂C(H)(CH₃)₂)— IIa-13

—N(C(CH₃)₃)— IIa-14

—CH₂— IIa-a14

—CH(OH)— IIa-15

—O— IIa-16

—C(O)— IIa-17

—NH— IIa-18

—S— IIa-19

—N(CH₃)— IIa-20

—N(CH₂CH₃)— IIa-21

—N(CH₂CH₂CH₃)— IIa-22

—N(CH₂CH₂CH₂CH₃)— IIa-23

—N(C(H)(CH₃)(CH₂CH₃))— IIa-24

—N(C(H)(CH₃)₂)— IIa-25

—N(CH₂C(H)(CH₃)₂)— IIa-26

—N(C(CH₃)₃)— IIa-27

—CH₂— IIa-a27

—CH(OH)— IIa-28

—O— IIa-29

—C(O)— IIa-30

—NH— IIa-31

—S— IIa-32

—N(CH₃)— IIa-33

—N(CH₂CH₃)— IIa-34

—N(CH₂CH₂CH₃)— IIa-35

—N(CH₂CH₂CH₂CH₃)— IIa-36

—N(C(H)(CH₃)(CH₂CH₃))— IIa-37

—N(C(H)(CH₃)₂)— IIa-38

—N(CH₂C(H)(CH₃)₂)— IIa-39

—N(C(CH₃)₃)— IIa-40

—CH₂— IIa-a40

—CH(OH)— IIa-41

—O— IIa-42

—C(O)— IIa-43

—NH— IIa-44

—S— IIa-45

—N(CH₃)— IIa-46

—N(CH₂CH₃)— IIa-47

—N(CH₂CH₂CH₃)— IIa-48

—N(CH₂CH₂CH₂CH₃)— IIa-49

—N(C(H)(CH₃)(CH₂CH₃))— IIa-50

—N(C(H)(CH₃)₂)— IIa-51

—N(CH₂C(H)(CH₃)₂)— IIa-52

—N(C(CH₃)₃)— IIa-53

—CH₂— IIa-a53

—CH(OH)— IIa-54

—O— IIa-55

—C(O)— IIa-56

—NH— IIa-57

—S— IIa-58

—N(CH₃)— IIa-59

—N(CH₂CH₃)— IIa-60

—N(CH₂CH₂CH₃)— IIa-61

—N(CH₂CH₂CH₂CH₃)— IIa-62

—N(C(H)(CH₃)(CH₂CH₃))— IIa-63

—N(C(H)(CH₃)₂)— IIa-64

—N(CH₂C(H)(CH₃)₂)— IIa-65

—N(C(CH₃)₃)— IIa-66

—CH₂— IIa-a66

—CH(OH)— IIa-67

—O— IIa-68

—C(O)— IIa-69

—NH— IIa-70

—S— IIa-71

—N(CH₃)— IIa-72

—N(CH₂CH₃)— IIa-73

—N(CH₂CH₂CH₃)— IIa-74

—N(CH₂CH₂CH₂CH₃)— IIa-75

—N(C(H)(CH₃)(CH₂CH₃))— IIa-76

—N(C(H)(CH₃)₂)— IIa-77

—N(CH₂C(H)(CH₃)₂)— IIa-78

—N(C(CH₃)₃)— IIa-79

—CH₂— IIa-a79

—CH(OH)— IIa-80

—O— IIa-81

—C(O)— IIa-82

—NH— IIa-83

—S— IIa-84

—N(CH₃)— IIa-85

—N(CH₂CH₃)— IIa-86

—N(CH₂CH₂CH₃)— IIa-87

—N(CH₂CH₂CH₂CH₃)— IIa-88

—N(C(H)(CH₃)(CH₂CH₃))— IIa-89

—N(C(H)(CH₃)₂)— IIa-90

—N(CH₂C(H)(CH₃)₂)— IIa-91

—N(C(CH₃)₃)— IIa-92

—CH₂— IIa-a92

—CH(OH)— IIa-93

—O— IIa-94

—C(O)— IIa-95

—NH— IIa-96

—S— IIa-97

—N(CH₃)— IIa-98

—N(CH₂CH₃)— IIa-99

—N(CH₂CH₂CH₃)— IIa-100

—N(CH₂CH₂CH₂CH₃)— IIa-101

—N(C(H)(CH₃)(CH₂CH₃))— IIa-102

—N(C(H)(CH₃)₂)— IIa-103

—N(CH₂C(H)(CH₃)₂)— IIa-104

—N(C(CH₃)₃)— IIa-105

—CH₂— IIa-a105

—CH(OH)— IIa-106

—O— IIa-107

—C(O)— IIa-108

—NH— IIa-109

—S— IIa-110

—N(CH₃)— IIa-111

—N(CH₂CH₃)— IIa-112

—N(CH₂CH₂CH₃)— IIa-113

—N(CH₂CH₂CH₂CH₃)— IIa-114

—N(C(H)(CH₃)(CH₂CH₃))— IIa-115

—N(C(H)(CH₃)₂)— IIa-116

—N(CH₂C(H)(CH₃)₂)— IIa-117

—N(C(CH₃)₃)— IIa-118

—CH₂— IIa-a118

—CH(OH)— IIa-119

—O— IIa-120

—C(O)— IIa-121

—NH— IIa-122

—S— IIa-123

—N(CH₃)— IIa-124

—N(CH₂CH₃)— IIa-125

—N(CH₂CH₂CH₃)— IIa-126

—N(CH₂CH₂CH₂CH₃)— IIa-127

—N(C(H)(CH₃)(CH₂CH₃))— IIa-128

—N(C(H)(CH₃)₂)— IIa-129

—N(CH₂C(H)(CH₃)₂)— IIa-130

—N(C(CH₃)₃)— IIa-131

—CH₂— IIa-a131

—CH(OH)— IIa-132

—O— IIa-133

—C(O)— IIa-134

—NH— IIa-135

—S— IIa-136

—N(CH₃)— IIa-137

—N(CH₂CH₃)— IIa-138

—N(CH₂CH₂CH₃)— IIa-139

—N(CH₂CH₂CH₂CH₃)— IIa-140

—N(C(H)(CH₃)(CH₂CH₃))— IIa-141

—N(C(H)(CH₃)₂)— IIa-142

—N(CH₂C(H)(CH₃)₂)— IIa-143

—N(C(CH₃)₃)— IIa-144

—CH₂— IIa-a144

—CH(OH)— IIa-145

—O— IIa-146

—C(O)— IIa-147

—NH— IIa-148

—S— IIa-149

—N(CH₃)— IIa-150

—N(CH₂CH₃)— IIa-151

—N(CH₂CH₂CH₃)— IIa-152

—N(CH₂CH₂CH₂CH₃)— IIa-153

—N(C(H)(CH₃)(CH₂CH₃))— IIa-154

—N(C(H)(CH₃)₂)— IIa-155

—N(CH₂C(H)(CH₃)₂)— IIa-156

—N(C(CH₃)₃)— IIa-157

—CH₂— IIa-a157

—CH(OH)— IIa-158

—O— IIa-159

—C(O)— IIa-160

—NH— IIa-161

—S— IIa-162

—N(CH₃)— IIa-163

—N(CH₂CH₃)— IIa-164

—N(CH₂CH₂CH₃)— IIa-165

—N(CH₂CH₂CH₂CH₃)— IIa-166

—N(C(H)(CH₃)(CH₂CH₃))— IIa-167

—N(C(H)(CH₃)₂)— IIa-168

—N(CH₂C(H)(CH₃)₂)— IIa-169

—N(C(CH₃)₃)— IIa-170

—CH₂— IIa-a170

—CH(OH)— IIa-171

—O— IIa-172

—C(O)— IIa-173

—NH— IIa-174

—S— IIa-175

—N(CH₃)— IIa-176

—N(CH₂CH₃)— IIa-177

—N(CH₂CH₂CH₃)— IIa-178

—N(CH₂CH₂CH₂CH₃)— IIa-179

—N(C(H)(CH₃)(CH₂CH₃))— IIa-180

—N(C(H)(CH₃)₂)— IIa-181

—N(CH₂C(H)(CH₃)₂)— IIa-182

—N(C(CH₃)₃)— IIa-183

—CH₂— IIa-a183

—CH(OH)— IIa-184

—O— IIa-185

—C(O)— IIa-186

—NH— IIa-187

—S— IIa-188

—N(CH₃)— IIa-189

—N(CH₂CH₃)— IIa-190

—N(CH₂CH₂CH₃)— IIa-191

—N(CH₂CH₂CH₂CH₃)— IIa-192

—N(C(H)(CH₃)(CH₂CH₃))— IIa-193

—N(C(H)(CH₃)₂)— IIa-194

—N(CH₂C(H)(CH₃)₂)— IIa-195

—N(C(CH₃)₃)— IIa-196

—CH₂— IIa-197

—CH(OH)— IIa-198

—O— IIa-199

—C(O)— IIa-200

—NH— IIa-201

—S— IIa-202

—N(CH₃)— IIa-203

—N(CH₂CH₃)— IIa-204

—N(CH₂CH₂CH₃)— IIa-205

—N(CH₂CH₂CH₂CH₃)— IIa-206

—N(C(H)(CH₃)(CH₂CH₃))— IIa-207

—N(C(H)(CH₃)₂)— IIa-208

—N(CH₂C(H)(CH₃)₂)— IIa-209

—N(C(CH₃)₃)—

and pharmaceutically acceptable salts thereof.

5.6 The Indenoisoquinolinone Analogs of Formula (IIb)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IIb) below:

and pharmaceutically acceptable salts thereof,wherein:

X and R¹ are as defined above for the compounds of Formula (IIb).

In one embodiment, X is —CH₂—. In another embodiment, X is —O—. Inanother embodiment, X is —C(O)—. In another embodiment, X is —NH—. Inanother embodiment, X is —N(C₁-C₄ alkyl)-. In another embodiment, X is—S—. In another embodiment, X is —CH(OH)—.

In one embodiment, n is 1. In another embodiment, n is 2.

In one embodiment, X is —CH₂— and n is 1.

In one embodiment, X is —CH₂— and n is 2.

In one embodiment, X is —CH(OH)— and n is 1.

In one embodiment, X is —CH(OH)— and n is 2.

In one embodiment, R² is —C₁-C₆ alkyl and R³ is —C(O)—(C₁-C₆alkylene)-(3- to 7-membered monocyclic heterocycle).

In one embodiment, R² is —H and R³ is —C(O)—(C₁-C₆ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, n is 1 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 1 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, n is 2 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 2 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, n is 1 and N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, X is —CH₂—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH₂—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is a nitrogen-containing3- to 7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH₂—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH(OH)—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In various embodiments, —R¹ is:

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IIb) in which n is 1 as set forth below:

Compound —R¹ X IIb-1

—CH₂— IIb-b1

—CH(OH)— IIb-2

—O— IIb-3

—C(O)— IIb-4

—NH— IIb-5

—S— IIb-6

—N(CH₃)— IIb-7

—N(CH₂CH₃)— IIb-8

—N(CH₂CH₂CH₃)— IIb-9

—N(CH₂CH₂CH₂CH₃)— IIb-10

—N(C(H)(CH₃)(CH₂CH₃))— IIb-11

—N(C(H)(CH₃)₂)— IIb-12

—N(CH₂C(H)(CH₃)₂)— IIb-13

—N(C(CH₃)₃)— IIb-14

—CH₂— IIb-b14

—CH(OH)— IIb-15

—O— IIb-16

—C(O)— IIb-17

—NH— IIb-18

—S— IIb-19

—N(CH₃)— IIb-20

—N(CH₂CH₃)— IIb-21

—N(CH₂CH₂CH₃)— IIb-22

—N(CH₂CH₂CH₂CH₃)— IIb-23

—N(C(H)(CH₃)(CH₂CH₃))— IIb-24

—N(C(H)(CH₃)₂)— IIb-25

—N(CH₂C(H)(CH₃)₂)— IIb-26

—N(C(CH₃)₃)— IIb-27

—CH₂— IIb-b27

—CH(OH)— IIb-28

—O— IIb-29

—C(O)— IIb-30

—NH— IIb-31

—S— IIb-32

—N(CH₃)— IIb-33

—N(CH₂CH₃)— IIb-34

—N(CH₂CH₂CH₃)— IIb-35

—N(CH₂CH₂CH₂CH₃)— IIb-36

—N(C(H)(CH₃)(CH₂CH₃))— IIb-37

—N(C(H)(CH₃)₂)— IIb-38

—N(CH₂C(H)(CH₃)₂)— IIb-39

—N(C(CH₃)₃)— IIb-40

—CH₂— IIb-b40

—CH(OH)— IIb-41

—O— IIb-42

—C(O)— IIb-43

—NH— IIb-44

—S— IIb-45

—N(CH₃)— IIb-46

—N(CH₂CH₃)— IIb-47

—N(CH₂CH₂CH₃)— IIb-48

—N(CH₂CH₂CH₂CH₃)— IIb-49

—N(C(H)(CH₃)(CH₂CH₃))— IIb-50

—N(C(H)(CH₃)₂)— IIb-51

—N(CH₂C(H)(CH₃)₂)— IIb-52

—N(C(CH₃)₃)— IIb-53

—CH₂— IIb-b53

—CH(OH)— IIb-54

—O— IIb-55

—C(O)— IIb-56

—NH— IIb-57

—S— IIb-58

—N(CH₃)— IIb-59

—N(CH₂CH₃)— IIb-60

—N(CH₂CH₂CH₃)— IIb-61

—N(CH₂CH₂CH₂CH₃)— IIb-62

—N(C(H)(CH₃)(CH₂CH₃))— IIb-63

—N(C(H)(CH₃)₂)— IIb-64

—N(CH₂C(H)(CH₃)₂)— IIb-65

—N(C(CH₃)₃)— IIb-66

—CH₂— IIb-b66

—CH(OH)— IIb-67

—O— IIb-68

—C(O)— IIb-69

—NH— IIb-70

—S— IIb-71

—N(CH₃)— IIb-72

—N(CH₂CH₃)— IIb-73

—N(CH₂CH₂CH₃)— IIb-74

—N(CH₂CH₂CH₂CH₃)— IIb-75

—N(C(H)(CH₃)(CH₂CH₃))— IIb-76

—N(C(H)(CH₃)₂)— IIb-77

—N(CH₂C(H)(CH₃)₂)— IIb-78

—N(C(CH₃)₃)— IIb-79

—CH₂— IIb-b79

—CH(OH)— IIb-80

—O— IIb-81

—C(O)— IIb-82

—NH— IIb-83

—S— IIb-84

—N(CH₃)— IIb-85

—N(CH₂CH₃)— IIb-86

—N(CH₂CH₂CH₃)— IIb-87

—N(CH₂CH₂CH₂CH₃)— IIb-88

—N(C(H)(CH₃)(CH₂CH₃))— IIb-89

—N(C(H)(CH₃)₂)— IIb-90

—N(CH₂C(H)(CH₃)₂)— IIb-91

—N(C(CH₃)₃)— IIb-92

—CH₂— IIb-b92

—CH(OH)— IIb-93

—O— IIb-94

—C(O)— IIb-95

—NH— IIb-96

—S— IIb-97

—N(CH₃)— IIb-98

—N(CH₂CH₃)— IIb-99

—N(CH₂CH₂CH₃)— IIb-100

—N(CH₂CH₂CH₂CH₃)— IIb-101

—N(C(H)(CH₃)(CH₂CH₃))— IIb-102

—N(C(H)(CH₃)₂)— IIb-103

—N(CH₂C(H)(CH₃)₂)— IIb-104

—N(C(CH₃)₃)— IIb-105

—CH₂— IIb-b105

—CH(OH)— IIb-106

—O— IIb-107

—C(O)— IIb-108

—NH— IIb-109

—S— IIb-110

—N(CH₃)— IIb-111

—N(CH₂CH₃)— IIb-112

—N(CH₂CH₂CH₃)— IIb-113

—N(CH₂CH₂CH₂CH₃)— IIb-114

—N(C(H)(CH₃)(CH₂CH₃))— IIb-115

—N(C(H)(CH₃)₂)— IIb-116

—N(CH₂C(H)(CH₃)₂)— IIb-117

—N(C(CH₃)₃)— IIb-118

—CH₂— IIb-b118

—CH(OH)— IIb-119

—O— IIb-120

—C(O)— IIb-121

—NH— IIb-122

—S— IIb-123

—N(CH₃)— IIb-124

—N(CH₂CH₃)— IIb-125

—N(CH₂CH₂CH₃)— IIb-126

—N(CH₂CH₂CH₂CH₃)— IIb-127

—N(C(H)(CH₃)(CH₂CH₃))— IIb-128

—N(C(H)(CH₃)₂)— IIb-129

—N(CH₂C(H)(CH₃)₂)— IIb-130

—N(C(CH₃)₃)— IIb-131

—CH₂— IIb-b131

—CH(OH)— IIb-132

—O— IIb-133

—C(O)— IIb-134

—NH— IIb-135

—S— IIb-136

—N(CH₃)— IIb-137

—N(CH₂CH₃)— IIb-138

—N(CH₂CH₂CH₃)— IIb-139

—N(CH₂CH₂CH₂CH₃)— IIb-140

—N(C(H)(CH₃)(CH₂CH₃))— IIb-141

—N(C(H)(CH₃)₂)— IIb-142

—N(CH₂C(H)(CH₃)₂)— IIb-143

—N(C(CH₃)₃)— IIb-144

—CH₂— IIb-b144

—CH(OH)— IIb-145

—O— IIb-146

—C(O)— IIb-147

—NH— IIb-148

—S— IIb-149

—N(CH₃)— IIb-150

—N(CH₂CH₃)— IIb-151

—N(CH₂CH₂CH₃)— IIb-152

—N(CH₂CH₂CH₂CH₃)— IIb-153

—N(C(H)(CH₃)(CH₂CH₃))— IIb-154

—N(C(H)(CH₃)₂)— IIb-155

—N(CH₂C(H)(CH₃)₂)— IIb-156

—N(C(CH₃)₃)— IIb-157

—CH₂— IIb-b157

—CH(OH)— IIb-158

—O— IIb-159

—C(O)— IIb-160

—NH— IIb-161

—S— IIb-162

—N(CH₃)— IIb-163

—N(CH₂CH₃)— IIb-164

—N(CH₂CH₂CH₃)— IIb-165

—N(CH₂CH₂CH₂CH₃)— IIb-166

—N(C(H)(CH₃)(CH₂CH₃))— IIb-167

—N(C(H)(CH₃)₂)— IIb-168

—N(CH₂C(H)(CH₃)₂)— IIb-169

—N(C(CH₃)₃)— IIb-170

—CH₂— IIb-b170

—CH(OH)— IIb-171

—O— IIb-172

—C(O)— IIb-173

—NH— IIb-174

—S— IIb-175

—N(CH₃)— IIb-176

—N(CH₂CH₃)— IIb-177

—N(CH₂CH₂CH₃)— IIb-178

—N(CH₂CH₂CH₂CH₃)— IIb-179

—N(C(H)(CH₃)(CH₂CH₃))— IIb-180

—N(C(H)(CH₃)₂)— IIb-181

—N(CH₂C(H)(CH₃)₂)— IIb-182

—N(C(CH₃)₃)— IIb-183

—CH₂— IIb-b183

—CH(OH)— IIb-184

—O— IIb-185

—C(O)— IIb-186

—NH— IIb-187

—S— IIb-188

—N(CH₃)— IIb-189

—N(CH₂CH₃)— IIb-190

—N(CH₂CH₂CH₃)— IIb-191

—N(CH₂CH₂CH₂CH₃)— IIb-192

—N(C(H)(CH₃)(CH₂CH₃))— IIb-193

—N(C(H)(CH₃)₂)— IIb-194

—N(CH₂C(H)(CH₃)₂)— IIb-195

—N(C(CH₃)₃)— IIb-196

—CH₂— IIb-197

—CH(OH)— IIb-198

—O— IIb-199

—C(O)— IIb-200

—NH— IIb-201

—S— IIb-202

—N(CH₃)— IIb-203

—N(CH₂CH₃)— IIb-204

—N(CH₂CH₂CH₃)— IIb-205

—N(CH₂CH₂CH₂CH₃)— IIb-206

—N(C(H)(CH₃)(CH₂CH₃))— IIb-207

—N(C(H)(CH₃)₂)— IIb-208

—N(CH₂C(H)(CH₃)₂)— IIb-209

—N(C(CH₃)₃)— IIb-210

—CH₂— IIb-211

—CH(OH)— IIb-212

—O— IIb-213

—C(O)— IIb-214

—NH— IIb-215

—S— IIb-216

—N(CH₃)— IIb-217

—N(CH₂CH₃)— IIb-218

—N(CH₂CH₂CH₃)— IIb-219

—N(CH₂CH₂CH₂CH₃)— IIb-220

—N(C(H)(CH₃)(CH₂CH₃))— IIb-221

—N(C(H)(CH₃)₂)— IIb-222

—N(CH₂C(H)(CH₃)₂)— IIb-223

—N(C(CH₃)₃)—

and pharmaceutically acceptable salts thereof.

5.7 The Indenoisoquinolinone Analogs of Formula (IIc)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IIc) below:

and pharmaceutically acceptable salts thereof,wherein:

X and R¹ are as defined above for the compounds of Formula (IIc).

In one embodiment, X is —CH₂—. In another embodiment, X is —O—. Inanother embodiment, X is —C(O)—. In another embodiment, X is —NH—. Inanother embodiment, X is —N(C₁-C₄ alkyl)-. In another embodiment, X is—S—. In another embodiment, X is —CH(OH)—.

In one embodiment, n is 1. In another embodiment, n is 2.

In one embodiment, X is —CH₂— and n is 1.

In one embodiment, X is —CH₂— and n is 2.

In one embodiment, X is —CH(OH)— and n is 1.

In one embodiment, X is —CH(OH)— and n is 2.

In one embodiment, R² is —C₁-C₆ alkyl and R³ is —C(O)—(C₁-C₆alkylene)-(3- to 7-membered monocyclic heterocycle).

In one embodiment, R² is —H and R³ is —C(O)—(C₁-C₆ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, n is 1 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 1 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, n is 2 and R³ is a nitrogen-containing 3- to7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In another embodiment, n is 2 and R³ is C₃-C₈ monocyclic cycloalkylsubstituted with one hydroxy-substituted C₁-C₅ alkyl.

In one embodiment, N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, n is 1 and N, R² and R³ are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, whichsubstituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆ alkyl, —(C₁-C₄alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀ alkyl, —(C₁-C₅alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted) C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle), or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle).

In one embodiment, X is —CH₂—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH₂—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is a nitrogen-containing3- to 7-membered monocyclic heterocycle which is substituted with one—C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH₂—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH₂—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1 and N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which substituted with one of —C₂-C₆ alkenyl, —C(O)—C₁-C₆alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl), —C₇-C₁₀alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂, -(cyano-substituted)C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)-(nitrogen-containing 3- to7-membered monocyclic heterocycle), or —(C₁-C₅ alkylene)-(3- to7-membered monocyclic heterocycle).

In one embodiment, X is —CH(OH)—, n is 1, and R² is C₃-C₈ monocycliccycloalkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, and R³ is C₃-C₈ monocycliccycloalkyl which is substituted with one hydroxy-substituted C₁-C₅alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one —C(O)O—C₁-C₆ alkyl.

In one embodiment, X is —CH(OH)—, n is 1, R² is —H, and R³ is C₃-C₈monocyclic cycloalkyl which is substituted with one hydroxy-substitutedC₁-C₅ alkyl.

In another embodiment, X is —CH(OH)—, n is 1 and R³ is —C(O)—C₁-C₆alkylene-(3- to 7-membered monocyclic heterocycle).

In various embodiments, —R¹ is:

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IIc) in which n is 1 as set forth below:

Compound —R¹ X IIc-1

—CH₂— IIc-c1

—CH(OH)— IIc-2

—O— IIc-3

—C(O)— IIc-4

—NH— IIc-5

—S— IIc-6

—N(CH₃)— IIc-7

—N(CH₂CH₃)— IIc-8

—N(CH₂CH₂CH₃)— IIc-9

—N(CH₂CH₂CH₂CH₃)— IIc-10

—N(C(H)(CH₃)(CH₂CH₃))— IIc-11

—N(C(H)(CH₃)₂)— IIc-12

—N(CH₂C(H)(CH₃)₂)— IIc-13

—N(C(CH₃)₃)— IIc-14

—CH₂— IIc-c14

—CH(OH)— IIc-15

—O— IIc-16

—C(O)— IIc-17

—NH— IIc-18

—S— IIc-19

—N(CH₃)— IIc-20

—N(CH₂CH₃)— IIc-21

—N(CH₂CH₂CH₃)— IIc-22

—N(CH₂CH₂CH₂CH₃)— IIc-23

—N(C(H)(CH₃)(CH₂CH₃))— IIc-24

—N(C(H)(CH₃)₂)— IIc-25

—N(CH₂C(H)(CH₃)₂)— IIc-26

—N(C(CH₃)₃)— IIc-27

—CH₂— IIc-c27

—CH(OH)— IIc-28

—O— IIc-29

—C(O)— IIc-30

—NH— IIc-31

—S— IIc-32

—N(CH₃)— IIc-33

—N(CH₂CH₃)— IIc-34

—N(CH₂CH₂CH₃)— IIc-35

—N(CH₂CH₂CH₂CH₃)— IIc-36

—N(C(H)(CH₃)(CH₂CH₃))— IIc-37

—N(C(H)(CH₃)₂)— IIc-38

—N(CH₂C(H)(CH₃)₂)— IIc-39

—N(C(CH₃)₃)— IIc-40

—CH₂— IIc-c40

—CH(OH)— IIc-41

—O— IIc-42

—C(O)— IIc-43

—NH— IIc-44

—S— IIc-45

—N(CH₃)— IIc-46

—N(CH₂CH₃)— IIc-47

—N(CH₂CH₂CH₃)— IIc-48

—N(CH₂CH₂CH₂CH₃)— IIc-49

—N(C(H)(CH₃)(CH₂CH₃))— IIc-50

—N(C(H)(CH₃)₂)— IIc-51

—N(CH₂C(H)(CH₃)₂)— IIc-52

—N(C(CH₃)₃)— IIc-53

—CH₂— IIc-c53

—CH(OH)— IIc-54

—O— IIc-55

—C(O)— IIc-56

—NH— IIc-57

—S— IIc-58

—N(CH₃)— IIc-59

—N(CH₂CH₃)— IIc-60

—N(CH₂CH₂CH₃)— IIc-61

—N(CH₂CH₂CH₂CH₃)— IIc-62

—N(C(H)(CH₃)(CH₂CH₃))— IIc-63

—N(C(H)(CH₃)₂)— IIc-64

—N(CH₂C(H)(CH₃)₂)— IIc-65

—N(C(CH₃)₃)— IIc-66

—CH₂— IIc-c66

—CH(OH)— IIc-67

—O— IIc-68

—C(O)— IIc-69

—NH— IIc-70

—S— IIc-71

—N(CH₃)— IIc-72

—N(CH₂CH₃)— IIc-73

—N(CH₂CH₂CH₃)— IIc-74

—N(CH₂CH₂CH₂CH₃)— IIc-75

—N(C(H)(CH₃)(CH₂CH₃))— IIc-76

—N(C(H)(CH₃)₂)— IIc-77

—N(CH₂C(H)(CH₃)₂)— IIc-78

—N(C(CH₃)₃)— IIc-79

—CH₂— IIc-c79

—CH(OH)— IIc-80

—O— IIc-81

—C(O)— IIc-82

—NH— IIc-83

—S— IIc-84

—N(CH₃)— IIc-85

—N(CH₂CH₃)— IIc-86

—N(CH₂CH₂CH₃)— IIc-87

—N(CH₂CH₂CH₂CH₃)— IIc-88

—N(C(H)(CH₃)(CH₂CH₃))— IIc-89

—N(C(H)(CH₃)₂)— IIc-90

—N(CH₂C(H)(CH₃)₂)— IIc-91

—N(C(CH₃)₃)— IIc-92

—CH₂— IIc-c92

—CH(OH)— IIc-93

—O— IIc-94

—C(O)— IIc-95

—NH— IIc-96

—S— IIc-97

—N(CH₃)— IIc-98

—N(CH₂CH₃)— IIc-99

—N(CH₂CH₂CH₃)— IIc-100

—N(CH₂CH₂CH₂CH₃)— IIc-101

—N(C(H)(CH₃)(CH₂CH₃))— IIc-102

—N(C(H)(CH₃)₂)— IIc-103

—N(CH₂C(H)(CH₃)₂)— IIc-104

—N(C(CH₃)₃)— IIc-105

—CH₂— IIc-c105

—CH(OH)— IIc-106

—O— IIc-107

—C(O)— IIc-108

—NH— IIc-109

—S— IIc-110

—N(CH₃)— IIc-111

—N(CH₂CH₃)— IIc-112

—N(CH₂CH₂CH₃)— IIc-113

—N(CH₂CH₂CH₂CH₃)— IIc-114

—N(C(H)(CH₃)(CH₂CH₃))— IIc-115

—N(C(H)(CH₃)₂)— IIc-116

—N(CH₂C(H)(CH₃)₂)— IIc-117

—N(C(CH₃)₃)— IIc-118

—CH₂— IIc-c118

—CH(OH)— IIc-119

—O— IIc-120

—C(O)— IIc-121

—NH— IIc-122

—S— IIc-123

—N(CH₃)— IIc-124

—N(CH₂CH₃)— IIc-125

—N(CH₂CH₂CH₃)— IIc-126

—N(CH₂CH₂CH₂CH₃)— IIc-127

—N(C(H)(CH₃)(CH₂CH₃))— IIc-128

—N(C(H)(CH₃)₂)— IIc-129

—N(CH₂C(H)(CH₃)₂)— IIc-130

—N(C(CH₃)₃)— IIc-131

—CH₂— IIc-c131

—CH(OH)— IIc-132

—O— IIc-133

—C(O)— IIc-134

—NH— IIc-135

—S— IIc-136

—N(CH₃)— IIc-137

—N(CH₂CH₃)— IIc-138

—N(CH₂CH₂CH₃)— IIc-139

—N(CH₂CH₂CH₂CH₃)— IIc-140

—N(C(H)(CH₃)(CH₂CH₃))— IIc-141

—N(C(H)(CH₃)₂)— IIc-142

—N(CH₂C(H)(CH₃)₂)— IIc-143

—N(C(CH₃)₃)— IIc-144

—CH₂— IIc-c144

—CH(OH)— IIc-145

—O— IIc-146

—C(O)— IIc-147

—NH— IIc-148

—S— IIc-149

—N(CH₃)— IIc-150

—N(CH₂CH₃)— IIc-151

—N(CH₂CH₂CH₃)— IIc-152

—N(CH₂CH₂CH₂CH₃)— IIc-153

—N(C(H)(CH₃)(CH₂CH₃))— IIc-154

—N(C(H)(CH₃)₂)— IIc-155

—N(CH₂C(H)(CH₃)₂)— IIc-156

—N(C(CH₃)₃)— IIc-157

—CH₂— IIc-c157

—CH(OH)— IIc-158

—O— IIc-159

—C(O)— IIc-160

—NH— IIc-161

—S— IIc-162

—N(CH₃)— IIc-163

—N(CH₂CH₃)— IIc-164

—N(CH₂CH₂CH₃)— IIc-165

—N(CH₂CH₂CH₂CH₃)— IIc-166

—N(C(H)(CH₃)(CH₂CH₃))— IIc-167

—N(C(H)(CH₃)₂)— IIc-168

—N(CH₂C(H)(CH₃)₂)— IIc-169

—N(C(CH₃)₃)— IIc-170

—CH₂— IIc-c170

—CH(OH)— IIc-171

—O— IIc-172

—C(O)— IIc-173

—NH— IIc-174

—S— IIc-175

—N(CH₃)— IIc-176

—N(CH₂CH₃)— IIc-177

—N(CH₂CH₂CH₃)— IIc-178

—N(CH₂CH₂CH₂CH₃)— IIc-179

—N(C(H)(CH₃)(CH₂CH₃))— IIc-180

—N(C(H)(CH₃)₂)— IIc-181

—N(CH₂C(H)(CH₃)₂)— IIc-182

—N(C(CH₃)₃)— IIc-183

—CH₂— IIc-c183

—CH(OH)— IIc-184

—O— IIc-185

—C(O)— IIc-186

—NH— IIc-187

—S— IIc-188

—N(CH₃)— IIc-189

—N(CH₂CH₃)— IIc-190

—N(CH₂CH₂CH₃)— IIc-191

—N(CH₂CH₂CH₂CH₃)— IIc-192

—N(C(H)(CH₃)(CH₂CH₃))— IIc-193

—N(C(H)(CH₃)₂)— IIc-194

—N(CH₂C(H)(CH₃)₂)— IIc-195

—N(C(CH₃)₃)— IIc-196

—CH₂— IIc-197

—CH(OH)— IIc-198

—O— IIc-199

—C(O)— IIc-200

—NH— IIc-201

—S— IIc-202

—N(CH₃)— IIc-203

—N(CH₂CH₃)— IIc-204

—N(CH₂CH₂CH₃)— IIc-205

—N(CH₂CH₂CH₂CH₃)— IIc-206

—N(C(H)(CH₃)(CH₂CH₃))— IIc-207

—N(C(H)(CH₃)₂)— IIc-208

—N(CH₂C(H)(CH₃)₂)— IIc-209

—N(C(CH₃)₃)—

and pharmaceutically acceptable salts thereof.

5.8 The Indenoisoquinolinone Analogs of Formula (IIIa)

The present invention provides the following IndenoisoquinolinoneAnalogs according to Formula (IIIa) as set forth below:

(IIIa)

Compound —R¹ IIIa-1

IIIa-2

IIIa-3

IIIa-4

IIIa-5

IIIa-6

IIIa-7

IIIa-8

IIIa-9

IIIa-10

IIIa-11

IIIa-12

IIIa-13

IIIa-14

IIIa-15

IIIa-16

IIIa-17

IIIa-18

IIIa-19

IIIa-20

IIIa-21

IIIa-22

IIIa-23

IIIa-24

and pharmaceutically acceptable salts thereof.

5.9 The Indenoisoquinolinone Analogs of Formula (IIIb)

The present invention provides the following IndenoisoquinolinoneAnalogs according to Formula (IIIb) as set forth below:

(IIIb)

Compound —R¹ IIIb-1

IIIb-2

IIIb-3

IIIb-4

IIIb-5

IIIb-6

IIIb-7

IIIb-8

IIIb-9

IIIb-10

IIIb-11

IIIb-12

IIIb-13

IIIb-14

IIIb-15

IIIb-16

IIIb-17

IIIb-18

IIIb-19

IIIb-20

IIIb-21

IIIb-22

IIIb-23

IIIb-24

and pharmaceutically acceptable salts thereof.

5.10 The Indenoisoquinolinone Analogs of Formula (IVa)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IVa), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (IVa).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, X is —O—. In one embodiment, X is —CH₂—. In oneembodiment, X is —C(O)—. In one embodiment, X is —NH—. In oneembodiment, X is —S—. In one embodiment, X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is independent of the other C₁-C₃alkyl.

In one embodiment, each C₁-C₃ alkyl is methyl.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH₂—.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH₂— and n is 1.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH(OH)— and n is 1.

In another embodiment, X is —CH(OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and n is 2.

In still another embodiment, X is —N((CH₂)-Z)- and n is 1.

In still another embodiment, X is —N((CH₂)-Z)- and n is 2.

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 1.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 2.

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and n is 2.

In still another embodiment, X is —N((CH₂)₂—OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—F)— and n is 2.

In still another embodiment, X is —N((CH₂)—F)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 2.

In still another embodiment, X is —N((CH₂)₂—OMe)- and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In one embodiment, n is 1 and X is —N(CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₃).

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(CH₂C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3;

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3; and

at least one C₁-C₃ alkyl is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))-, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is —C₃-C₈ monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, which issubstituted with a hydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂)— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, which issubstituted with a nitrogen-containing 3- to 7-membered monocyclicheterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IVa) as set forth below:

(IVa)

Compound —R¹ X IVa-1 —OC(Me)(Me)—CH₂—N(Et)(Et) —O— IVa-2—OC(Me)(Me)—CH₂—N(Et)(Et) —CH₂— IVa-3 —OC(Me)(Me)—CH₂—N(Et)(Et) —C(O)—IVa-4 —OC(Me)(Me)—CH₂—N(Et)(Et) —NH— IVa-5 —OC(Me)(Me)—CH₂—N(Et)(Et) —S—IVa-6 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₃)— IVa-7 —OC(Me)(Me)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVa-8 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVa-9—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVa-10—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVa-11—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVa-12—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVa-13—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVa-14 —OC(Me)(Me)—CH₂—N(Et)(Et)—CH(OH)— IVa-15 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVa-16 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVa-17—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVa-18—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVa-19—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVa-20—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVa-21—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVa-22—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVa-23—OC(Me)(Et)—CH₂—N(Et)(Et) —O— IVa-24 —OC(Me)(Et)—CH₂—N(Et)(Et) —CH₂—IVa-25 —OC(Me)(Et)—CH₂—N(Et)(Et) —C(O)— IVa-26 —OC(Me)(Et)—CH₂—N(Et)(Et)—NH— IVa-27 —OC(Me)(Et)—CH₂—N(Et)(Et) —S— IVa-28—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₃)— IVa-29 —OC(Me)(Et)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVa-30 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVa-31—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVa-32—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVa-33—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVa-34—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVa-35—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVa-36 —OC(Me)(Et)—CH₂—N(Et)(Et)—CH(OH)— IVa-37 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVa-38 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVa-39—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVa-40—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVa-41—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVa-42—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVa-43—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVa-44—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVa-45—OC(Me)(Pr)—CH₂—N(Et)(Et) —O— IVa-46 —OC(Me)(Pr)—CH₂—N(Et)(Et) —CH₂—IVa-47 —OC(Me)(Pr)—CH₂—N(Et)(Et) —C(O)— IVa-48 —OC(Me)(Pr)—CH₂—N(Et)(Et)—NH— IVa-49 —OC(Me)(Pr)—CH₂—N(Et)(Et) —S— IVa-50—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₃)— IVa-51 —OC(Me)(Pr)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVa-52 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVa-53—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVa-54—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVa-55—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVa-56—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVa-57—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVa-58 —OC(Me)(Pr)—CH₂—N(Et)(Et)—CH(OH)— IVa-59 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVa-60 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVa-61—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVa-62—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVa-63—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVa-64—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVa-65—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVa-66—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVa-67—OC(Me)(i-Pr)—CH₂— —O— N(H)(cyclopropyl) IVa-68 —OC(Me)(i-Pr)—CH₂— —CH₂—N(H)(cyclopropyl) IVa-69 —OC(Me)(i-Pr)—CH₂— —C(O)— N(H)(cyclopropyl)IVa-70 —OC(Me)(i-Pr)—CH₂— —NH— N(H)(cyclopropyl) IVa-71—OC(Me)(i-Pr)—CH₂— —S— N(H)(cyclopropyl) IVa-72 —OC(Me)(i-Pr)—CH₂——N(CH₃)— N(H)(cyclopropyl) IVa-73 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₃)—N(H)(cyclopropyl) IVa-74 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₃)—N(H)(cyclopropyl) IVa-75 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₂CH₃)—N(H)(cyclopropyl) IVa-76 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)(CH₂CH₃))—N(H)(cyclopropyl) IVa-77 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)₂)—N(H)(cyclopropyl) IVa-78 —OC(Me)(i-Pr)—CH₂— —N(CH₂C(H)(CH₃)₂)—N(H)(cyclopropyl) IVa-79 —OC(Me)(i-Pr)—CH₂— —N(C(CH₃)₃)—N(H)(cyclopropyl) IVa-80 —OC(Me)(i-Pr)—CH₂— —CH(OH)— N(H)(cyclopropyl)IVa-81 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OH)— N(H)(cyclopropyl)IVa-82 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—F)— N(H)(cyclopropyl)IVa-83 —OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OH)— N(H)(cyclopropyl) IVa-84—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—F)— N(H)(cyclopropyl) IVa-85—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVa-86—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—CF₃)— N(H)(cyclopropyl) IVa-87—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVa-88—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—CF₃)— N(H)(cyclopropyl)

and pharmaceutically acceptable salts thereof.

5.11 The Indenoisoquinolinone Analogs of Formula (IVb)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IVb), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (IVb).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, X is —O—. In one embodiment, X is —CH₂—. In oneembodiment, X is —C(O)—. In one embodiment, X is —NH—. In oneembodiment, X is —S—. In one embodiment, X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is independent of the other C₁-C₃alkyl.

In one embodiment, each C₁-C₃ alkyl is methyl.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH₂—.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH₂— and n is 1.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH(OH)— and n is 1.

In another embodiment, X is —CH(OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and n is 2.

In still another embodiment, X is —N((CH₂)-Z)- and n is 1.

In still another embodiment, X is —N((CH₂)-Z)- and n is 2.

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 1.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 2.

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and n is 2.

In still another embodiment, X is —N((CH₂)₂—OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—F)— and n is 2.

In still another embodiment, X is —N((CH₂)—F)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 2.

In still another embodiment, X is —N((CH₂)₂—OMe)- and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In one embodiment, n is 1 and X is —N(CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₃).

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(CH₂C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3;

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3; and

at least one C₁-C₃ alkyl is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl; and at least one R²is —C₃-C₈ monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))-, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl is methyl, wherein N andboth R² groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle, which is substituted with a hydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, which issubstituted with a nitrogen-containing 3- to 7-membered monocyclicheterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IVb) as set forth below:

(IVb)

Compound —R¹ X IVb-1 —OC(Me)(Me)—CH₂—N(Et)(Et) —O— IVb-2—OC(Me)(Me)—CH₂—N(Et)(Et) —CH₂— IVb-3 —OC(Me)(Me)—CH₂—N(Et)(Et) —C(O)—IVb-4 —OC(Me)(Me)—CH₂—N(Et)(Et) —NH— IVb-5 —OC(Me)(Me)—CH₂—N(Et)(Et) —S—IVb-6 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₃)— IVb-7 —OC(Me)(Me)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVb-8 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVb-9—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVb-10—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVb-11—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVb-12—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVb-13—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVb-14 —OC(Me)(Me)—CH₂—N(Et)(Et)—CH(OH)— IVb-15 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVb-16 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVb-17—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVb-18—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVb-19—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVb-20—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVb-21—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVb-22—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVb-23—OC(Me)(Et)—CH₂—N(Et)(Et) —O— IVb-24 —OC(Me)(Et)—CH₂—N(Et)(Et) —CH₂—IVb-25 —OC(Me)(Et)—CH₂—N(Et)(Et) —C(O)— IVb-26 —OC(Me)(Et)—CH₂—N(Et)(Et)—NH— IVb-27 —OC(Me)(Et)—CH₂—N(Et)(Et) —S— IVb-28—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₃)— IVb-29 —OC(Me)(Et)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVb-30 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVb-31—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVb-32—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVb-33—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVb-34—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVb-35—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVb-36 —OC(Me)(Et)—CH₂—N(Et)(Et)—CH(OH)— IVb-37 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVb-38 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVb-39—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVb-40—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVb-41—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVb-42—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVb-43—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVb-44—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVb-45—OC(Me)(Pr)—CH₂—N(Et)(Et) —O— IVb-46 —OC(Me)(Pr)—CH₂—N(Et)(Et) —CH₂—IVb-47 —OC(Me)(Pr)—CH₂—N(Et)(Et) —C(O)— IVb-48 —OC(Me)(Pr)—CH₂—N(Et)(Et)—NH— IVb-49 —OC(Me)(Pr)—CH₂—N(Et)(Et) —S— IVb-50—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₃)— IVb-51 —OC(Me)(Pr)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVb-52 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVb-53—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVb-54—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVb-55—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVb-56—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVb-57—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVb-58 —OC(Me)(Pr)—CH₂—N(Et)(Et)—CH(OH)— IVb-59 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVb-60 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVb-61—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVb-62—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVb-63—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVb-64—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVb-65—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVb-66—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVb-67—OC(Me)(i-Pr)—CH₂— —O— N(H)(cyclopropyl) IVb-68 —OC(Me)(i-Pr)—CH₂— —CH₂—N(H)(cyclopropyl) IVb-69 —OC(Me)(i-Pr)—CH₂— —C(O)— N(H)(cyclopropyl)IVb-70 —OC(Me)(i-Pr)—CH₂— —NH— N(H)(cyclopropyl) IVb-71—OC(Me)(i-Pr)—CH₂— —S— N(H)(cyclopropyl) IVb-72 —OC(Me)(i-Pr)—CH₂——N(CH₃)— N(H)(cyclopropyl) IVb-73 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₃)—N(H)(cyclopropyl) IVb-74 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₃)—N(H)(cyclopropyl) IVb-75 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₂CH₃)—N(H)(cyclopropyl) IVb-76 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)(CH₂CH₃))—N(H)(cyclopropyl) IVb-77 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)₂)—N(H)(cyclopropyl) IVb-78 —OC(Me)(i-Pr)—CH₂— —N(CH₂C(H)(CH₃)₂)—N(H)(cyclopropyl) IVb-79 —OC(Me)(i-Pr)—CH₂— —N(C(CH₃)₃)—N(H)(cyclopropyl) IVb-80 —OC(Me)(i-Pr)—CH₂— —CH(OH)— N(H)(cyclopropyl)IVb-81 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OH)— N(H)(cyclopropyl)IVb-82 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—F)— N(H)(cyclopropyl)IVb-83 —OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OH)— N(H)(cyclopropyl) IVb-84—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—F)— N(H)(cyclopropyl) IVb-85—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVb-86—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—CF₃)— N(H)(cyclopropyl) IVb-87—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVb-88—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—CF₃)— N(H)(cyclopropyl)

and pharmaceutically acceptable salts thereof.

5.12 The Indenoisoquinolinone Analogs of Formula (IVc)

The present invention provides Indenoisoquinolinone Analogs according toFormula (IVc), below:

and pharmaceutically acceptable salts thereof,wherein X and R¹ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (IVc).

In one embodiment, X is —N(CH₃)—. In another embodiment, X is—N(CH₂CH₃)—. In another embodiment, X is —N(CH₂CH₂CH₃)—. In anotherembodiment, X is —N(CH₂CH₂CH₂CH₃)—. In another embodiment, X is—N(C(H)(CH₃)(CH₂CH₃))—. In another embodiment, X is —N(C(H)(CH₃)₂)—. Inanother embodiment, X is —N(CH₂C(H)(CH₃)₂)—. In another embodiment, X is—N(C(CH₃)₃)—.

In one embodiment, X is —O—. In one embodiment, X is —CH₂—. In oneembodiment,

X is —C(O)—. In one embodiment, X is —NH—. In one embodiment, X is —S—.In one embodiment, X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is independent of the other C₁-C₃alkyl.

In one embodiment, each C₁-C₃ alkyl is methyl.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH₂—.

In one embodiment, each C₁-C₃ alkyl is methyl and X is —CH(OH)—.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH₂— and n is 1.

In one embodiment, each C₁-C₃ alkyl is methyl, X is —CH(OH)— and n is 1.

In another embodiment, X is —CH(OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)-Z)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)₂-Z)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)-Z)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)-Z)-.

In another embodiment, X is —N((CH₂)-Z)-.

In another embodiment, X is —N((CH₂)₂-Z)-.

In another embodiment, X is —N((CH₂)_(q)-Z)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)-Z)- and n is 2.

In still another embodiment, X is —N((CH₂)-Z)- and n is 1.

In still another embodiment, X is —N((CH₂)-Z)- and n is 2.

In one embodiment, Z is —CF₃.

In another embodiment, Z is —F.

In yet another embodiment, Z is —OH.

In still another embodiment, Z is —O—CH₃.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OH)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 1.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OH)— and n is 2.

In one embodiment, X is —N((CH₂)_(q)—OH)—.

In another embodiment, X is —N((CH₂)₂—OH)—.

In another embodiment, X is —N((CH₂)_(q)—OH)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OH)— and n is 2.

In still another embodiment, X is —N((CH₂)₂—OH)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—F)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—F)— n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—F)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—F)—.

In another embodiment, X is —N((CH₂)—F)—.

In another embodiment, X is —N((CH₂)_(q)—F)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—F)— and n is 2.

In still another embodiment, X is —N((CH₂)—F)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)-.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—OMe)- and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)₂—OMe)- and n is 1.

In one embodiment, X is —N((CH₂)_(q)—OMe)-.

In another embodiment, X is —N((CH₂)₂—OMe)-.

In another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—OMe)- and n is 2.

In still another embodiment, X is —N((CH₂)₂—OMe)- and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)—.

In another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 1.

In yet another embodiment, X is —N(C(O)N(H)—(CH₂)_(p)—CF₃)— and n is 2.

In still another embodiment, X is —N(C(O)N(H)—(CH₂)—CF₃)— and n is 1.

In one embodiment, X is —N((CH₂)_(q)—CF₃)—.

In another embodiment, X is —N((CH₂)—CF₃)—.

In another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 1.

In yet another embodiment, X is —N((CH₂)_(q)—CF₃)— and n is 2.

In still another embodiment, X is —N((CH₂)—CF₃)— and n is 1.

In one embodiment, n is 1.

In another embodiment, n is 2.

In yet another embodiment, n is 3.

In a further embodiment, n is 4, 5, or 6.

In yet a further embodiment, n is 7, 8, or 9.

In still a further embodiment, n is 10.

In one embodiment, p is 1.

In another embodiment, p is 2.

In yet another embodiment, p is an integer ranging from 2 to 5.

In one embodiment, q is 1.

In another embodiment, q is 2.

In yet another embodiment, q is an integer ranging from 2 to 5.

In one embodiment, n is 1 and X is —N(CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₃).

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(CH₂CH₂CH₂CH₃)—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)(CH₂CH₃))—.

In another embodiment, n is 1 and X is —N(C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(CH₂C(H)(CH₃)₂)—.

In another embodiment, n is 1 and X is —N(C(CH₃)₃)—.

In one embodiment, one R² is —H, and the other R² is —C₁-C₆ alkyl.

In another embodiment, each R² is —C₁-C₆ alkyl.

In another embodiment, each R² is -methyl.

In various embodiments, —N(R²)(R²) is:

In other embodiments, —N(R²)(R²) is:

In some embodiments, —N(R²)(R²) is

In still other embodiments, —N(R²)(R²) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(R²)(R²) is

In various embodiments, —N(Z₃)(Z₄) is:

In other embodiments, —N(Z₃)(Z₄) is:

In some embodiments, —N(Z₃)(Z₄) is

In still other embodiments, —N(Z₃)(Z₄) is

-   -   —N(CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₃)(CH₃),    -   —N(CH₂CH₂CH₂CH₃)(CH₃),    -   —NH—CH₂CH₂CH₂CH₃, or    -   —NH—CH₂CH₂—O—CH₃.

In some embodiments, —N(Z₃)(Z₄) is

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))-, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3;

each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or -phenyl, each ofwhich other than hydrogen is unsubstituted or substituted with one ormore of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), where Z₃ andZ₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅ alkylene)-O—C₁-C₅alkyl, each of which other than hydrogen is unsubstituted or substitutedwith one or more of -halo, —OH or —NH₂;

or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —C₁-C₅ alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl;

or N and both R² groups are taken together to form a nitrogen-containing3- to 7-membered monocyclic heterocycle which is unsubstituted orsubstituted with one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅alkylene)-phenyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo,-(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —(C₁-C₅alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅ alkylene)-OP(O)(OH)₂,—(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl, —OC(O)—C₁-C₅ alkyl,—(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)NH—C₁-C₅alkyl, —C(O)NH₂, or —NO₂, wherein each occurrence of R^(a) isindependently —H, -benzyl, or —C₁-C₁₀ alkyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—;

n is an integer ranging from 1 to 3; and

at least one C₁-C₃ alkyl is methyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is ethyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is propyl.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl; and at least one R²is —C₃-C₈ monocyclic cycloalkyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; at least one C₁-C₃ alkyl is methyl;and at least one R² is cyclohexyl.

In yet another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle.

In one embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂—or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl is methyl, wherein N andboth R² groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle, which is substituted with a hydroxyl.

In another embodiment, X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—,—N(CH₂ CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—,—N(CH₂C(H)(CH₃)₂— or —N(C(CH₃)₃)—; and at least one C₁-C₃ alkyl ismethyl, wherein N and both R² groups are taken together to form anitrogen-containing 3- to 7-membered monocyclic heterocycle, which issubstituted with a nitrogen-containing 3- to 7-membered monocyclicheterocycle.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (IVc) as set forth below:

(IVc)

Compound —R¹ X IVb-1 —OC(Me)(Me)—CH₂—N(Et)(Et) —O— IVc-2—OC(Me)(Me)—CH₂—N(Et)(Et) —CH₂— IVc-3 —OC(Me)(Me)—CH₂—N(Et)(Et) —C(O)—IVc-4 —OC(Me)(Me)—CH₂—N(Et)(Et) —NH— IVc-5 —OC(Me)(Me)—CH₂—N(Et)(Et) —S—IVc-6 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₃)— IVc-7 —OC(Me)(Me)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVc-8 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVc-9—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVc-10—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVc-11—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVc-12—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVc-13—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVc-14 —OC(Me)(Me)—CH₂—N(Et)(Et)—CH(OH)— IVc-15 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVc-16 —OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVc-17—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVc-18—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVc-19—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVc-20—OC(Me)(Me)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVc-21—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVc-22—OC(Me)(Me)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVc-23—OC(Me)(Et)—CH₂—N(Et)(Et) —O— IVc-24 —OC(Me)(Et)—CH₂—N(Et)(Et) —CH₂—IVc-25 —OC(Me)(Et)—CH₂—N(Et)(Et) —C(O)— IVc-26 —OC(Me)(Et)—CH₂—N(Et)(Et)—NH— IVc-27 —OC(Me)(Et)—CH₂—N(Et)(Et) —S— IVc-28—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₃)— IVc-29 —OC(Me)(Et)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVc-30 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVc-31—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVc-32—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVc-33—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVc-34—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVc-35—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVc-36 —OC(Me)(Et)—CH₂—N(Et)(Et)—CH(OH)— IVc-37 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVc-38 —OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVc-39—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVc-40—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVc-41—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVc-42—OC(Me)(Et)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVc-43—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVc-44—OC(Me)(Et)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVc-45—OC(Me)(Pr)—CH₂—N(Et)(Et) —O— IVc-46 —OC(Me)(Pr)—CH₂—N(Et)(Et) —CH₂—IVc-47 —OC(Me)(Pr)—CH₂—N(Et)(Et) —C(O)— IVc-48 —OC(Me)(Pr)—CH₂—N(Et)(Et)—NH— IVc-49 —OC(Me)(Pr)—CH₂—N(Et)(Et) —S— IVc-50—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₃)— IVc-51 —OC(Me)(Pr)—CH₂—N(Et)(Et)—N(CH₂CH₃)— IVc-52 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₃)— IVc-53—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂CH₂CH₂CH₃)— IVc-54—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)(CH₂CH₃))— IVc-55—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(H)(CH₃)₂)— IVc-56—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂C(H)(CH₃)₂)— IVc-57—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(CH₃)₃)— IVc-58 —OC(Me)(Pr)—CH₂—N(Et)(Et)—CH(OH)— IVc-59 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OH)—IVc-60 —OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—F)— IVc-61—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OH)— IVc-62—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—F)— IVc-63—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—OCH₃)— IVc-64—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(CH₂—CH₂—CF₃)— IVc-65—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—OCH₃)— IVc-66—OC(Me)(Pr)—CH₂—N(Et)(Et) —N(C(O)N(H)—CH₂—CH₂—CF₃)— IVc-67—OC(Me)(i-Pr)—CH₂— —O— N(H)(cyclopropyl) IVc-68 —OC(Me)(i-Pr)—CH₂— —CH₂—N(H)(cyclopropyl) IVc-69 —OC(Me)(i-Pr)—CH₂— —C(O)— N(H)(cyclopropyl)IVc-70 —OC(Me)(i-Pr)—CH₂— —NH— N(H)(cyclopropyl) IVc-71—OC(Me)(i-Pr)—CH₂— —S— N(H)(cyclopropyl) IVc-72 —OC(Me)(i-Pr)—CH₂——N(CH₃)— N(H)(cyclopropyl) IVc-73 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₃)—N(H)(cyclopropyl) IVc-74 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₃)—N(H)(cyclopropyl) IVc-75 —OC(Me)(i-Pr)—CH₂— —N(CH₂CH₂CH₂CH₃)—N(H)(cyclopropyl) IVc-76 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)(CH₂CH₃))—N(H)(cyclopropyl) IVc-77 —OC(Me)(i-Pr)—CH₂— —N(C(H)(CH₃)₂)—N(H)(cyclopropyl) IVc-78 —OC(Me)(i-Pr)—CH₂— —N(CH₂C(H)(CH₃)₂)—N(H)(cyclopropyl) IVc-79 —OC(Me)(i-Pr)—CH₂— —N(C(CH₃)₃)—N(H)(cyclopropyl) IVc-80 —OC(Me)(i-Pr)—CH₂— —CH(OH)— N(H)(cyclopropyl)IVc-81 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OH)— N(H)(cyclopropyl)IVc-82 —OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—F)— N(H)(cyclopropyl)IVc-83 —OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OH)— N(H)(cyclopropyl) IVc-84—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—F)— N(H)(cyclopropyl) IVc-85—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVc-86—OC(Me)(i-Pr)—CH₂— —N(CH₂—CH₂—CF₃)— N(H)(cyclopropyl) IVc-87—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—OCH₃)— N(H)(cyclopropyl) IVc-88—OC(Me)(i-Pr)—CH₂— —N(C(O)N(H)—CH₂—CH₂—CF₃)— N(H)(cyclopropyl)

and pharmaceutically acceptable salts thereof.

5.13 The Indenoisoquinolinone Analogs of Formula (Va)

The present invention provides Indenoisoquinolinone Analogs according toFormula (Va), below:

and pharmaceutically acceptable salts thereof,wherein R¹, X and Y′ are as defined above for the IndenoisoquinolinoneAnalogs of Formula (Va).

In one embodiment, R¹ is —(CH₂)_(n)—NHR² and R² is a —C₃-C₈ monocycliccycloalkyl.

In another embodiment, R¹ is —(CH₂)_(n)—NHR² and R² is a —C₃-C₈monocyclic cycloalkyl substituted with one or more of-(hydroxy-substituted) C₁-C₅ alkyl.

In one embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl, and X is fluoro.

In one embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl, and X is chloro.

In one embodiment, R¹ is —(CH₂)_(n)—NHR² and R² is cyclopentyl.

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl substituted with one or more of -(hydroxy-substituted) C₁-C₅alkyl, and X is fluoro .

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is cyclopentylsubstituted with one or more of -(hydroxy-substituted C₁-C₅ alkyl), andX is fluoro .

In one embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl, and Y′ is fluoro.

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl substituted with one or more of -(hydroxy-substituted C₁-C₅alkyl), and Y′ is fluoro .

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a —C₃-C₈ monocycliccycloalkyl substituted with one or more of -(hydroxy-substituted) C₁-C₅alkyl, and X and Y′ are fluoro.

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a 3- to 7-memberedmonocyclic heterocycle, and X is fluoro.

In another embodiment, R¹ is —(CH₂)_(n)—NHR², R² is a 3- to 7-memberedmonocyclic heterocycle, and Y′ is fluoro.

In another embodiment, R¹ is —(CH₂)_(n)—NHR² and R² istetrahydropyranyl.

In one embodiment, R² is tetrahydropyranyl, or cyclopentyl which isunsubstituted or substituted with one or more of -(hydroxy-substitutedC₁-C₅ alkyl).

In another embodiment, one of X and Y′ is fluoro.

Illustrative examples of the Indenoisoquinolinone Analogs include thecompounds of Formula (Va) as set forth below:

(Va)

Compound —R¹ X Y' Va-1

—Cl, at position 4 —H Va-2

—F, at position 2 —H Va-3

—F, at position 3 —H Va-4

—F, at position 4 —H Va-5

—F, at position 3 —H Va-6

—F, at position 1 —H Va-7

—F, at position 1 —H Va-8

—F, at position 2 —H Va-9

—H —F, at position 8 Va-10

—F, at position 3 —F, at position 8

5.14 Methods for Making Indenoisoquinolinone Analogs

Methods useful for making the Indenoisoquinolinone Analogs are set forthin the Examples below and generalized in Schemes 1-7.

wherein n and each R² is defined above for the IndenoisoquinolinoneAnalogs of Formula (IIa), (IIb), (IIc), (IIIa), (IIIb), (IVa), (IVb) or(IVc), and X is —Br, —I, —Cl, —O-Ts, —O-Ms, —O-Triflate, or —O-Acetate.

As shown in Scheme 1, a compound of formula 1 can be reacted withmethanol in the presence of an acid, for example, sulphuric acid, toprovide a compound of formula 2. The compound of formula 2 can then bereacted with cyanide to provide a compound of formula 3. The compound offormula 3 can be brominated using, for example, N-bromosuccinimide, toprovide a compound of formula 4. The compound of formula 4 can then bereacted with homophthalic anhydride to provide a compound of formula 5.The compound of formula 5 can then be reduced, for example with lithiumaluminum hydride (LAH), to provide a compound of formula 6.

As shown in Scheme 2, an indenoisoquinolinone compound of formula 8 canbe reacted with hydrochloric acid or hydrobromic acid in the presence offormaldehyde to provide a halomethyl compound of formula 9. The compoundof formula 9 can then be reacted with an amine of formula NH(R²)(R³) toprovide an Indenoisoquinolinone Analog of Formula (IIb), whereinR¹=—(CH₂)—N(R²)(R³), wherein each R² and R³ are as defined above.Alternatively, the compound of formula 9 can be reacted with anappropriate amine to provide an Indenoisoquinolinone Analog of Formula(IIIb) or (IVb).

A compound of formula 6 can be reacted with a reagent 6a to provide acompound of formula 7 (see, e.g., Scheme 1). Suitable reagents 6ainclude, but are not limited to, PBr₃, HBr, HI, SOCl₂, Ts-Cl, pyrene,MsCl, CF₃SO₂Cl, acetic anhydride, acetyl chloride or NEt₃. The compoundof formula 7 can then be reacted with an amine of formula NH(R²)(R³) toprovide an Indenoisoquinolinone Analog of Formula (IIa), (IIb) or (IIc)wherein R¹=—(CH₂)_(n)—N(R²)(R³), wherein n, R² and R³ are as definedabove. Alternatively, the compound of formula 7 can be reacted with anappropriate amine to provide an Indenoisoquinolinone Analog of Formula(IIIa) or (IIIb). Using similar methods, Indenoisoquinolinone Analogs ofFormula (IVa), (IVb) or (IVc) can also be obtained using an appropriateanalog of the compound of formula 1, as would be apparent to one ofordinary skill in the art.

wherein n is defined above for the Indenoisoquinolinone Analogs ofFormula (Ia), (Ib), (Ic), (IIa), (IIIb) or (IIc) and X′ is —OH, —SH,—NHC(O)OMe, or —N(C₁-C₄ alkyl). As set forth in Scheme 3, a compound offormula 10 is reacted with a compound of formula 11 in the presence oftriethylamine to provide a compound of formula 12, wherein X is —O—,—S—, —N(C(O)OMe)-, or —N(C₁-C₄ alkyl)-. The compound of formula 12 canthen be converted to provide an Indenoisoquinolinone Analog of Formula(Ia), (Ib), (Ic), (Ia), (IIb) or (IIc), e.g., using procedures outlinedin Scheme 1 and/or 2. The compound of formula 12, wherein X is—N(C(O)OMe)-, can be deprotected, for example using hydrazine, toprovide a compound, wherein X is —N(H)—. Using similar methods,Indenoisoquinolinone Analogs of Formula (IVa), (IVb) or (IVc) can alsobe obtained using an appropriate analog of the compound of formula 1, aswould be apparent to one of ordinary skill in the art.

wherein X′ is —OH, —SH, or NHC(O)OMe or —N(C₁-C₄ alkyl).

As set forth in Scheme 4, a compound of formula 13 is reacted with acompound of formula 11, to provide a compound of formula 14, wherein Xis —O—, —S—, —N(C(O)OMe)-, or —N(C₁-C₄ alkyl)-. The compound of formula14 is then converted to provide an Indenoisoquinolinone Analog ofFormula (Ia), (Ib), (Ic), wherein R¹=−O—(CH₂)_(m)—N(R²)(R²) or anIndenoisoquinolinone Analog of Formula (IVa), (IVb) or (IVc), forexample using methods described in Schemes 1 and/or 5.

wherein X, m, n, each R² and each C₁-C₃ alkyl is defined above for theIndenoisoquinolinone Analogs of Formula (Ia), (Ib), (Ic), (IVa), (IVb)or (IVc) and A is a halogen.

As set forth in Scheme 5, a compound of formula 14 is demethylated, forexample using boron tribromide, to provide a compound of formula 15. Acompound of formula 15 is then reacted in the presence of base withA(CH₂)_(m)NR²R² to provide the compound of the general formula 15a, anIndenoisoquinolinone Analog of Formula (Ia), (Ib), or (Ic), whereinR¹=—O—(CH₂)_(m)—N(R²)(R²). Alternatively, a compound of formula 15 isreacted in the presence of base with A-C(C₁-C₃ alkyl)₂(CH₂)_(n)NR²R² toprovide the compound of the general formula 15b, an IndenoisoquinolinoneAnalog of Formula (IVa), (IVb), or (IVc).

wherein R¹ is as defined above for the Indenoisoquinolinone Analogs ofFormula (IIa), (IIb), (IIc), (IVa), (IVb) or (IVc).

As set forth in Scheme 6, compounds of the general formula 16, which canbe prepared, for example, according to Schemes 1 or 2, can be oxidizedto provide a compound of the general formula 17, which is anIndenoisoquinolinone Analog of Formula (IIa), (IIb), (IIc), (IVa), (IVb)or (IVc), wherein X is —C(O)—. In one embodiment, the oxidation isachieved using O₂ and dimethylsulfoxide. In one aspect, the O₂ is thatwhich is present in air. In another embodiment, the oxidation isachieved using Cerium(IV) triflate (Ce(OTf)₄). Optional protectinggroups can be used (Greene et al., Protective Groups in OrganicSynthesis (3^(rd) ed. 1999)). For example, where R¹ is —(CH₂)_(n)—OH,protecting groups such as —SiEt₃, can be used to protect the R¹ hydroxylgroup during the oxidation and can then be removed, for example with anacid. The compound of the general formula 17, can be reduced, forexample with sodium borohydride or lithium aluminum hydride, to providethe compound of the general formula 18, which is an IndenoisoquinolinoneAnalog of Formula (IIa), (IIb), (IIc), (IVa), (IVb) or (IVc), wherein Xis —CH(OH)—.

As set forth in Scheme 7, Indenoisoquinolinone Analogs of Formula (Va)can be prepared, for example, as illustrated in part (1) of the schemeby reacting compound 19 with either compounds 20 or 23 to yieldcompounds 21 and 24, respectively. Compounds 21 and 24 can then bereacted with the selected amine to form compounds 22 and 25respectively. Compounds 22 and 25 are representative of anIndenoisoquinolinone Analog of Formula (Va). In part (2) of the scheme,reaction of compound 26 under suitable conditions and in the presence ofhomophthalic anhydride and the desired amine yields compound 27, whichis an Indenoisoquinolinone Analog of Formula of Formula (Va).

5.15 Treatment or Prevention of a Condition

In accordance with the invention, an Indenoisoquinolinone Analog isuseful for treatment or prevention of a Condition as set forth below.

5.8.1 Treatment or Prevention of an Inflammatory Disease

The Indenoisoquinolinone Analogs are useful for treating or preventingan inflammatory disease. An inflammatory disease can arise where thereis an inflammation of the body tissue. These include local inflammatoryresponses and systemic inflammation. Examples of inflammatory diseasesinclude, but are not limited to, lupus; pancreatitis; maculardegeneration; chronic obstructive pulmonary disease; organ transplantrejection; a chronic inflammatory disease of a joint, includingarthritis, rheumatoid arthritis, osteoarthritis and a bone diseaseassociated with increased bone resorption; an inflammatory bowel diseasesuch as ileitis, ulcerative colitis, Barrett's syndrome, and Crohn'sdisease; an inflammatory lung disease such as asthma, adult respiratorydistress syndrome, and chronic obstructive airway disease; aninflammatory disease of the eye including corneal dystrophy, trachoma,onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis; achronic inflammatory disease of the gum, including gingivitis andperiodontitis; tuberculosis; leprosy; an inflammatory disease of thekidney including a uremic complication, glomerulonephritis andnephrosis; an inflammatory disease of the skin includingsclerodermatitis, psoriasis and eczema; an inflammatory disease of thecentral nervous system, including a chronic demyelinating disease of thenervous system, multiple sclerosis, AIDS-related neurodegeneration andAlzheimer's disease, infectious meningitis, encephalomyelitis,Huntington's disease, amyotrophic lateral sclerosis and viral orautoimmune encephalitis; as well as any other disease that can have asignificant inflammatory component, including preeclampsia, chronicliver failure, and brain and spinal cord trauma. The inflammatorydisease can also be a systemic inflammation of the body, exemplified bygram-positive or gram negative shock, hemorrhagic or anaphylactic shock,or shock induced by cancer chemotherapy in response to pro-inflammatorycytokines, e.g., shock associated with pro-inflammatory cytokines. Suchshock can be induced, e.g., by a chemotherapeutic agent that isadministered as a treatment for cancer.

In one embodiment, the inflammatory disease is an inflammatory diseaseof a joint, a chronic inflammatory disease of the gum, an inflammatorybowel disease, an inflammatory lung disease, an inflammatory disease ofthe central nervous system, an inflammatory disease of the eye,gram-positive shock, gram negative shock, Rickettsial shock, fungalshock, hemorrhagic shock, anaphylactic shock, traumatic shock orchemotherapeutic shock.

5.8.2 Treatment or Prevention of a Reperfusion Injury

The Indenoisoquinolinone Analogs are useful for treating or preventing areperfusion injury. Reperfusion refers to the process whereby blood-flowin the blood vessels is resumed following ischemia, such as occursfollowing constriction or obstruction of the vessel. Reperfusion injurycan result following a naturally occurring episode, such as a myocardialinfarction, stroke, or during a surgical procedure where blood flow invessels is intentionally or unintentionally blocked. Examples ofreperfusion injuries include, but are not limited to, intestinalreperfusion injury, myocardial reperfusion injury, and reperfusioninjury resulting from cardiopulmonary bypass surgery, aortic aneurysmrepair surgery, carotid endarterectomy surgery, and hemorrhagic shock.

In one embodiment, the reperfusion injury results from cardiopulmonarybypass surgery, aortic aneurysm repair surgery, carotid endarterectomysurgery or hemorrhagic shock.

In another embodiment, the reperfusion injury is stroke or myocardialinfarction.

5.8.3 Treatment or Prevention of Reoxygenation Injury Resulting fromOrgan Transplantation

The Indenoisoquinolinone Analogs are useful for treating or preventingreoxygenation injury resulting from organ transplantation. Examples ofreoxygenation injuries include, but are not limited to, transplantationof one or more of the following: heart, lung, liver, kidney, pancreas,intestine and cornea.

In one embodiment, reoxygenation injury resulting from organtransplantation occurs during the organ transplantation.

The Indenoisoquinolinone Analogs are also useful for treating orpreventing allograph rejection. Accordingly, the invention providesmethods for treating or preventing allograph rejection, comprisingadministering an effective amount of an Indenoisoquinolinone Analog to asubject in need thereof. In one embodiment, the methods further compriseadministering an effective amount of another agent useful for treatingor preventing allograph rejection. The other agent includes, but is notlimited to, SK-506 and cyclosporine.

5.8.4 Treatment or Prevention of an Ischemic Condition

The Indenoisoquinolinone Analogs are useful for treating or preventingan ischemic condition. Examples of ischemic conditions include, but arenot limited to, stable angina, unstable angina, myocardial ischemia,hepatic ischemia, mesenteric artery ischemia, ischemic heart disease,intestinal ischemia, critical limb ischemia, chronic critical limbischemia, cerebral ischemia, acute cardiac ischemia, and an ischemicdisease of the central nervous system, such as stroke or cerebralischemia.

In one embodiment, the ischemic condition is myocardial ischemia, stableangina, unstable angina, stroke, ischemic heart disease or cerebralischemia.

5.8.5 Treatment or Prevention of Renal Failure

The Indenoisoquinolinone Analogs are useful for treating or preventingrenal failure.

In one embodiment, the renal failure is chronic renal failure.

In another embodiment, the renal failure is acute renal failure.

5.8.6 Treatment or Prevention of a Vascular Disease

The Indenoisoquinolinone Analogs are useful for treating or preventing avascular disease other than a cardiovascular disease. Examples ofvascular diseases include, but are not limited to, hemorrahgic stroke,peripheral arterial occlusion, thromboangitis obliterans, Reynaud'sdisease and phenomenon, acrocyanosis, erythromelalgia, venousthrombosis, varicose veins, arteriovenous fistula, lymphedema, andlipedema.

In embodiment, the vascular disease is peripheral arterial occlusion,thromboangitis obliterans, Reynaud's disease and phenomenon,acrocyanosis, erythromelalgia, venous thrombosis, varicose veins,arteriovenous fistula, lymphedema or lipedema.

5.8.7 Treatment or Prevention of a Cardiovascular Disease

The Indenoisoquinolinone Analogs are useful for treating or preventing acardiovascular disease. Examples of cardiovascular diseases include, butare not limited to, congestive heart failure (such as chronic or acuteheart failure), atherosclerosis, hypercholesterolemia, circulatoryshock, cardiomyopathy, cardiac transplant, myocardial infarction, and acardiac arrhythmia, such as atrial fibrillation, supraventriculartachycardia, atrial flutter, and paroxysmal atrial tachycardia.

In one embodiment, the cardiovascular disease is chronic heart failure.

In another embodiment, the cardiovascular disease is acute heartfailure.

In yet another embodiment, the cardiovascular disease is cardiacarrhythmia.

In still another embodiment, the cardiac arrhythmia is atrialfibrillation, supraventricular tachycardia, atrial flutter or paroxysmalatrial tachycardia.

In one embodiment, the cardiovascular disease is chronic heart failure,atrial fibrillation, supraventricular tachycardia, atrial flutter orparoxysmal atrial tachycardia.

5.8.8 Treatment or Prevention of Diabetes Mellitus or a DiabeticComplication

The Indenoisoquinolinone Analogs are useful for treating or preventingdiabetes mellitus or one or more of its complications. Examples ofdiabetes mellitus include, but are not limited to, Type I diabetes(Insulin Dependent Diabetes Mellitus), Type II diabetes (Non-InsulinDependent Diabetes Mellitus), gestational diabetes, autoimmune diabetes,insulinopathies, diabetes due to pancreatic disease, diabetes associatedwith other endocrine diseases (such as Cushing's Syndrome, acromegaly,pheochromocytoma, glucagonoma, primary aldosteronism orsomatostatinoma), Type A insulin resistance syndrome, Type B insulinresistance syndrome, lipatrophic diabetes, and diabetes induced byβ-cell toxins.

The Indenoisoquinolinone Analogs are useful for treating or preventing acomplication of diabetes mellitus. Examples of complications of diabetesmellitus include, but are not limited to, diabetic cataract, glaucoma,retinopathy, nephropathy (such as microalbuminuria or progressivediabetic nephropathy), polyneuropathy, gangrene of the feet,immune-complex vasculitis, systemic lupus erythematosus (SLE),atherosclerotic coronary arterial disease, peripheral arterial disease,nonketotic hyperglycemic-hyperosmolar coma, mononeuropathies, autonomicneuropathy, foot ulcers, joint problems, and a skin or mucous membranecomplication (such as an infection, a shin spot, a candidal infection ornecrobiosis lipoidica diabeticorumobesity), hyperlipidemia,hypertension, syndrome of insulin resistance, coronary artery disease,retinopathy, neuropathy (such as diabetic neuropathy, polyneuropathy ormononeuropathy), autonomic neuropathy, a foot ulcer, a joint problem, afungal infection, cardiomyopathy, and a bacterial infection.

In one embodiment diabetes mellitus is Type I diabetes mellitus or TypeII diabetes mellitus.

5.8.9 Treatment or Prevention of a Neurodegenerative Disease

The Indenoisoquinolinone Analogs are useful for treating or preventing aneurodegenerative disease. Examples of neurodegenerative diseasesinclude, but are not limited to, Alzheimer's disease, Parkinson'sdisease and amyotrophic lateral sclerosis.

5.8.10 Treatment or Prevention of Cancer

The Indenoisoquinolinone Analogs are useful for treating or preventingcancer.

Accordingly, the invention provides methods for treating or preventingcancer, comprising administering an effective amount of anIndenoisoquinolinone Analog to a subject in need thereof. In oneembodiment, the methods further comprise administering an effectiveamount of another anticancer agent.

Examples of cancers include, but are not limited to, the cancersdisclosed below in Table 1 and metastases thereof.

TABLE 1 Solid tumors, including but not limited to: fibrosarcomamyxosarcoma liposarcoma chondrosarcoma osteogenic sarcoma chordomaangiosarcoma endotheliosarcoma lymphangiosarcomalymphangioendotheliosarcoma synovioma mesothelioma Ewing's tumorleiomyosarcoma rhabdomyosarcoma colon cancer colorectal cancer kidneycancer pancreatic cancer bone cancer breast cancer ovarian cancerprostate cancer esophageal cancer stomach cancer oral cancer nasalcancer throat cancer squamous cell carcinoma basal cell carcinomaadenocarcinoma sweat gland carcinoma sebaceous gland carcinoma papillarycarcinoma papillary adenocarcinomas cystadenocarcinoma medullarycarcinoma bronchogenic carcinoma renal cell carcinoma hepatoma bile ductcarcinoma choriocarcinoma seminoma embryonal carcinoma Wilms' tumorcervical cancer uterine cancer testicular cancer small cell lungcarcinoma bladder carcinoma lung cancer epithelial carcinoma skin cancermelanoma metastatic melanoma neuroblastoma retinoblastoma blood-bornecancers, including but not limited to: acute lymphoblastic leukemia(“ALL”) acute lymphoblastic B-cell leukemia acute lymphoblastic T-cellleukemia acute myeloblastic leukemia (“AML”) acute promyelocyticleukemia (“APL”) acute monoblastic leukemia acute erythroleukemicleukemia acute megakaryoblastic leukemia acute myelomonocytic leukemiaacute nonlymphocyctic leukemia acute undifferentiated leukemia chronicmyelocytic leukemia (“CML”) chronic lymphocytic leukemia (“CLL”) hairycell leukemia multiple myeloma acute and chronic leukemias:lymphoblastic myelogenous lymphocytic myelocytic leukemias Lymphomas:Hodgkin's disease non-Hodgkin's Lymphoma Multiple myeloma Waldenström'smacroglobulinemia Heavy chain disease Polycythemia vera Central nervoussystem lymphomas CNS and Brain cancers: glioma pilocytic astrocytomaastrocytoma anaplastic astrocytoma glioblastoma multiformemedulloblastoma craniopharyngioma ependymoma pinealoma hemangioblastomaacoustic neuroma oligodendroglioma meningioma vestibular schwannomaadenoma metastatic brain tumor meningioma spinal tumor medulloblastoma

In one embodiment, the cancer is lung cancer, breast cancer, colorectalcancer, prostate cancer, a leukemia, a lymphoma, non-Hodgkin's lymphoma,skin cancer, a brain cancer, a cancer of the central nervous system,ovarian cancer, uterine cancer, stomach cancer, pancreatic cancer,esophageal cancer, kidney cancer, liver cancer, or a head and neckcancer.

In another embodiment, the cancer is metastatic cancer.

In yet another embodiment, the cancer is brain cancer or melanoma.

In one embodiment, the brain cancer is metastatic brain cancer or aglioma.

In one embodiment, the glioma is pilocytic astrocytoma, astrocytoma,anaplastic astrocytoma or glioblastoma multiforme.

In one embodiment, the cancer is homologous-recombination deficient,such as BRCA-1 or BRCA-2 deficient, or is deficient in one or moreproteins of the Fanconi family.

In one embodiment, the deficiency is caused by a genetic mutation. Inanother embodiment, the phenotype resulting from the deficiency iscaused by abnormally low expression of BRCA-1 or BRCA-2 protein. Inanother embodiment, the phenotype resulting from the deficiency iscaused by abnormally low expression of one or more proteins of theFanconi family.

In still another embodiment, the subject in need of treatment haspreviously undergone or is presently undergoing treatment for cancer.The treatment includes, but is not limited to, chemotherapy, radiationtherapy, surgery or immunotherapy, such as administration of a cancervaccine.

The Indenoisoquinolinone Analogs are also useful for treating orpreventing a cancer caused by a virus. Such viruses include humanpapilloma virus, which can lead to cervical cancer (see, e.g.,Hernandez-Avila et al., Archives of Medical Research (1997) 28:265-271);Epstein-Barr virus (EBV), which can lead to lymphoma (see, e.g.,Herrmann et al., J Pathol (2003) 199(2):140-5); hepatitis B or C virus,which can lead to liver carcinoma (see, e.g., El-Serag, J ClinGastroenterol (2002) 35(5 Suppl 2):S72-8); human T cell leukemia virus(HTLV)-I, which can lead to T-cell leukemia (see e.g., Mortreux et al.,Leukemia (2003) 17(1):26-38); human herpesvirus-8 infection, which canlead to Kaposi's sarcoma (see, e.g., Kadow et al., Curr Opin InvestigDrugs (2002) 3(11):1574-9); and Human Immune deficiency Virus (HIV)infection, which can lead to cancer as a consequence of immunodeficiency(see, e.g., Dal Maso et al., Lancet Oncol (2003) 4(2):110-9).

5.8.10.1 Prophylactic Methods for Cancer

The Indenoisoquinolinone Analogs are also useful for preventing cancer,or preventing progression of a cancer, including but not limited to thecancers listed in Table 1. Such prophylactic use includes that in whichnon-neoplastic cell growth such as hyperplasia, metaplasia, or mostspecifically, dysplasia has occurred.

Alternatively or in addition to the presence of abnormal cell growthcharacterized as hyperplasia, metaplasia, or dysplasia, the presence ofone or more characteristics of a transformed phenotype, or of amalignant phenotype, displayed in vivo or displayed in vitro by a cellsample from a subject, can indicate the desirability of prophylactic ortherapeutic administration of an Indenoisoquinolinone Analog. Suchcharacteristics of a transformed phenotype include morphology changes,looser substratum attachment, loss of contact inhibition, loss ofanchorage dependence, protease release, increased sugar transport,decreased serum requirement, expression of fetal antigens, disappearanceof the 250,000 dalton cell surface protein, etc. (see also id., at pp.84-90 for characteristics associated with a transformed or malignantphenotype).

In a specific embodiment, leukoplakia, a benign-appearing hyperplasticor dysplastic lesion of the epithelium, or Bowen's disease, a carcinomain situ, is treatable or preventable according to the present methods.

In another embodiment, fibrocystic disease (cystic hyperplasia, mammarydysplasia, specifically adenosis (benign epithelial hyperplasia)) istreatable or preventable according to the present methods.

In other embodiments, a subject that has one or more of the followingpredisposing factors for malignancy can be treated by administration ofan effective amount of an

Indenoisoquinolinone Analog: a chromosomal translocation associated witha malignancy (e.g., the Philadelphia chromosome for chronic myelogenousleukemia; t(14;18) for follicular lymphoma); familial polyposis orGardner's syndrome; benign monoclonal gammopathy; a first degree kinshipwith persons having a cancer or precancerous disease showing a Mendelian(genetic) inheritance pattern (e.g., familial polyposis of the colon,Gardner's syndrome, hereditary exostosis, polyendocrine adenomatosis,medullary thyroid carcinoma with amyloid production andpheochromocytoma, Peutz-Jeghers syndrome, neurofibromatosis of VonRecklinghausen, retinoblastoma, carotid body tumor, cutaneousmelanocarcinoma, intraocular melanocarcinoma, xeroderma pigmentosum,ataxia telangiectasia, Chediak-Higashi syndrome, albinism, Fanconi'saplastic anemia, and Bloom's syndrome); and exposure to carcinogens(e.g., smoking, second-hand smoke exposure, and inhalation of orcontacting with certain chemicals).

5.8.10.2 Combination Chemotherapy for the Treatment of Cancer

In one aspect, the present methods for treating or preventing cancer canfurther comprise the administration of another anticancer agent.

In one embodiment, the present invention provides methods for treatingor preventing cancer, comprising the administration of an effectiveamount of an Indenoisoquinolinone Analog and another anticancer agent toa subject in need thereof.

The Indenoisoquinolinone Analog and another anticancer agent can beadministered concurrently. In this embodiment, the IndenoisoquinolinoneAnalog and another anticancer agent can be administered within the samecomposition, or can be administered from different compositions, via thesame or different routes of administration.

In another embodiment, the Indenoisoquinolinone Analog is administeredduring a time when the other anticancer agent exerts its prophylactic ortherapeutic effect, or vice versa.

In another embodiment, the Indenoisoquinolinone Analog or otheranticancer agent are administered in doses commonly employed when suchagents are used as monotherapy for the treatment of cancer.

In one embodiment, the Indenoisoquinolinone Analog or other anticanceragent are administered in doses that are lower than the doses commonlyemployed when such agents are used as monotherapy for the treatment ofcancer.

In another embodiment, the Indenoisoquinolinone Analog and otheranticancer agent act synergistically and are administered in doses thatare lower than the doses commonly employed when such agents are used asmonotherapy for the treatment of cancer.

The dosage of the Indenoisoquinolinone Analog or other anticancer agentadministered as well as the dosing schedule can depend on variousparameters, including, but not limited to, the cancer being treated, thesubject's general health, and the administering physician's discretion.

An Indenoisoquinolinone Analog can be administered prior to (e.g., 5minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before),concurrently with, or subsequent to (e.g., 5 minutes, 15 minutes, 30minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks,5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of theother anticancer agent, to a subject in need thereof. In variousembodiments an Indenoisoquinolinone Analog and the other anticanceragent are administered 1 minute apart, 10 minutes apart, 30 minutesapart, less than 1 hour apart, 1 hour apart, 1 hour to 2 hours apart, 2hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hoursapart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10hours to 11 hours apart, 11 hours to 12 hours apart, no more than 24hours apart or no more than 48 hours apart. In one embodiment, anIndenoisoquinolinone Analog and the other anticancer agent areadministered within 3 hours. In another embodiment, anIndenoisoquinolinone Analog and the other anticancer agent areadministered at 1 minute to 24 hours apart.

In one embodiment, an effective amount of an Indenoisoquinolinone Analogand an effective amount of other anticancer agent are present in thesame composition. In one embodiment, this composition is useful for oraladministration. In another embodiment, this composition is useful forintravenous administration.

In one embodiment, the compositions comprise an amount of anIndenoisoquinolinone Analog and the other anticancer agent whichtogether are effective to treat or prevent cancer.

In another embodiment, the compositions comprise an effective amount oftemozolomide, procarbazine, dacarbazine, interleukin-2, irinotecan, ordoxorubicin, a physiologically acceptable carrier or vehicle, and aneffective amount of an Indenoisoquinolinone Analog.

In one embodiment, the amount of an Indenoisoquinolinone Analog and theother anticancer agent is at least about 0.01% of the combinedcombination chemotherapy agents by weight of the composition. Whenintended for oral administration, this amount can be varied from about0.1% to about 80% by weight of the composition. Some oral compositionscan comprise from about 4% to about 50% of combined amount of anIndenoisoquinolinone Analog and the other anticancer agent by weight ofthe composition. Other compositions of the present invention areprepared so that a parenteral dosage unit contains from about 0.01% toabout 2% by weight of the composition.

Cancers that can be treated or prevented by administering anIndenoisoquinolinone Analog and the other anticancer agent include, butare not limited to, the list of cancers set forth above in Table 1.

In one embodiment, the cancer is brain cancer.

In specific embodiments, the brain cancer is pilocytic astrocytoma,astrocytoma, anaplastic astrocytoma, glioblastoma multiforme or ametastatic brain tumor.

In one embodiment, the cancer is melanoma.

In a specific embodiment, the melanoma is metastatic melanoma.

The Indenoisoquinolinone Analog and other anticancer agent can actadditively or synergistically. A synergistic combination of anIndenoisoquinolinone Analog and the other anticancer agent, might allowthe use of lower dosages of one or both of these agents and/or lessfrequent administration of the agents to a subject with cancer. Theability to utilize lower dosages of one or both of theIndenoisoquinolinone Analog and other anticancer agent and/or toadminister the agents less frequently can reduce any toxicity associatedwith the administration of the agents to a subject without reducing theefficacy of the agents in the treatment of cancer. In addition, asynergistic effect might result in the improved efficacy of these agentsin the treatment of cancer and/or the reduction of any adverse orunwanted side effects associated with the use of either agent alone.

In one embodiment, the administration of an effective amount of anIndenoisoquinolinone Analog and an effective amount of anotheranticancer agent inhibits the resistance of a cancer to the otheranticancer agent. In one embodiment, the cancer is a tumor.

Suitable other anticancer agents useful in the methods and compositionsof the present invention include, but are not limited to temozolomide, atopoisomerase I inhibitor, procarbazine, dacarbazine, gemcitabine,capecitabine, methotrexate, taxol, taxotere, mercaptopurine,thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide,nitrosoureas, cisplatin, carboplatin, mitomycin, dacarbazine,procarbizine, etoposide, teniposide, campathecins, bleomycin,doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin,mitoxantrone, L-asparaginase, doxorubicin, epirubicin, 5-fluorouracil,taxanes such as docetaxel and paclitaxel, leucovorin, levamisole,irinotecan, estramustine, etoposide, nitrogen mustards, BCNU,nitrosoureas such as carmustine and lomustine, vinca alkaloids such asvinblastine, vincristine and vinorelbine, platinum complexes such ascisplatin, carboplatin and oxaliplatin, imatinib mesylate,hexamethylmelamine, topotecan, tyrosine kinase inhibitors, tyrphostinsherbimycin A, genistein, erbstatin, and lavendustin A.

In one embodiment, the other anticancer agent is, but is not limited to,a drug listed in Table 2.

TABLE 2 Alkylating agents Nitrogen mustards: Cyclophosphamide IfosfamideTrofosfamide Chlorambucil Nitrosoureas: Carmustine (BCNU) Lomustine(CCNU) Alkylsulphonates: Busulfan Treosulfan Triazenes: DacarbazineProcarbazine Temozolomide Platinum containing complexes: CisplatinCarboplatin Aroplatin Oxaliplatin Plant Alkaloids Vinca alkaloids:Vincristine Vinblastine Vindesine Vinorelbine Taxoids: PaclitaxelDocetaxel DNA Topoisomerase Inhibitors Epipodophyllins: EtoposideTeniposide Topotecan 9-aminocamptothecin Camptothecin CrisnatolMitomycins: Mitomycin C Anti-metabolites Anti-folates: DHFR inhibitors:Methotrexate Trimetrexate IMP dehydrogenase Inhibitors: Mycophenolicacid Tiazofurin Ribavirin EICAR Ribonuclotide reductase HydroxyureaInhibitors: Deferoxamine Pyrimidine Analogs: Uracil Analogs:5-Fluorouracil Fluoxuridine Doxifluridine Ralitrexed Cytosine Analogs:Cytarabine (ara C) Cytosine arabinoside Fludarabine GemcitabineCapecitabine Purine Analogs: Mercaptopurine Thioguanine DNAAntimetabolites: 3-HP 2′-deoxy-5-fluorouridine 5-HP alpha-TGDRaphidicolin glycinate ara-C 5-aza-2′-deoxycytidine beta-TGDRcyclocytidine guanazole inosine glycodialdehyde macebecin IIPyrazoloimidazole Hormonal therapies: Receptor antagonists:Anti-estrogen: Tamoxifen Raloxifene Megestrol LHRH agonists: GoscrclinLeuprolide acetate Anti-androgens: Flutamide BicalutamideRetinoids/Deltoids Vitamin A derivative: Cis-retinoic acid All-transretinoic acid (ATRA-IV) Vitamin D3 Analogs: EB 1089 CB 1093 KH 1060Photodynamic therapies: Vertoporfin (BPD-MA) PhthalocyaninePhotosensitizer Pc4 Demethoxy-hypocrellin A (2BA-2-DMHA) Cytokines:Interferon-α Interferon-β Interferon-γ Tumor necrosis factorInterleukin-2 Angiogenesis Inhibitors: Angiostatin (plasminogenfragment) antiangiogenic antithrombin III Angiozyme ABT-627 Bay 12-9566Benefin Bevacizumab BMS-275291 cartilage-derived inhibitor (CDI) CAICD59 complement fragment CEP-7055 Col 3 Combretastatin A-4 Endostatin(collagen XVIII fragment) Fibronectin fragment Gro-beta HalofuginoneHeparinases Heparin hexasaccharide fragment HMV833 Human chorionicgonadotropin (hCG) IM-862 Interferon alpha/beta/gamma Interferoninducible protein (IP- 10) Interleukin-12 Kringle 5 (plasminogenfragment) Marimastat Metalloproteinase inhibitors (TIMPs)2-Methoxyestradiol MMI 270 (CGS 27023A) MoAb IMC-1C11 Neovastat NM-3Panzem PI-88 Placental ribonuclease inhibitor Plasminogen activatorinhibitor Platelet factor-4 (PF4) Prinomastat Prolactin 16 kD fragmentProliferin-related protein (PRP) PTK 787/ZK 222594 Retinoids SolimastatSqualamine SS 3304 SU 5416 SU6668 SU11248 Tetrahydrocortisol-STetrathiomolybdate Thalidomide Thrombospondin-1 (TSP-1) TNP-470Transforming growth factor-beta (TGF-β) Vasculostatin Vasostatin(calreticulin fragment) ZD6126 ZD 6474 farnesyl transferase inhibitors(FTI) Bisphosphonates Antimitotic agents: Allocolchicine Halichondrin BColchicine colchicine derivative dolstatin 10 Maytansine RhizoxinThiocolchicine trityl cysteine Others: Isoprenylation inhibitors:Dopaminergic neurotoxins: 1-methyl-4-phenylpyridinium ion Cell cycleinhibitors: Staurosporine Actinomycins: Actinomycin D DactinomycinBleomycins: Bleomycin A2 Bleomycin B2 Peplomycin Anthracyclines:Daunorubicin Doxorubicin (adriamycin) Idarubicin Epirubicin PirarubicinZorubicin Mitoxantrone MDR inhibitors: Verapamil Ca²⁺ ATPase inhibitors:Thapsigargin

Other additional anticancer agents that are useful in the compositionsand methods of the present invention include, but are not limited to:acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin;aldesleukin; altretamine; ambomycin; ametantrone acetate;aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase;asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa;bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin;bleomycin sulfate; brequinar sodium; bropirimine; busulfan;cactinomycin; calusterone; caracemide; carbetimer; carboplatin;carmustine; carubicin hydrochloride; carzelesin; cedefingol;chlorambucil; cirolemycin; cisplatin; cladribine; crisnatol mesylate;cyclophosphamide; cytarabine; dacarbazine; dactinomycin; daunorubicinhydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguaninemesylate; diaziquone; docetaxel; doxorubicin; doxorubicin hydrochloride;droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin;edatrexate; eflornithine hydrochloride; elsamitrucin; enloplatin;enpromate; epipropidine; epirubicin hydrochloride; erbulozole;esorubicin hydrochloride; estramustine; estramustine phosphate sodium;etanidazole; etoposide; etoposide phosphate; etoprine; fadrozolehydrochloride; fazarabine; fenretinide; floxuridine; fludarabinephosphate; fluorouracil; fluorocitabine; fosquidone; fostriecin sodium;gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride;ifosfamide; ilmofosine; interleukin-2 (including recombinantinterleukin-2, or rIL2), interferon alfa-2a; interferon alfa-2β;interferon alfa-n1; interferon alfa-n3; interferon beta-Iα; interferongamma-Iβ; iproplatin; irinotecan hydrochloride; lanreotide acetate;letrozole; leuprolide acetate; liarozole hydrochloride; lometrexolsodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine;mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate;melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium;metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin;mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride;mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran;paclitaxel; pegaspargase; peliomycin; pentamustine; peplomycin sulfate;perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride;plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine;procarbazine hydrochloride; puromycin; puromycin hydrochloride;pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride;semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermaniumhydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin;sulofenur; talisomycin; tecogalan sodium; tegafur; teloxantronehydrochloride; temoporfin; teniposide; teroxirone; testolactone;thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifenecitrate; trestolone acetate; triciribine phosphate; trimetrexate;trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracilmustard; uredepa; vapreotide; verteporfin; vinblastine sulfate;vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate;vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate;vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin;zinostatin; zorubicin hydrochloride.

Further anticancer drugs that are useful in the methods and compositionsof the invention include, but are not limited to: 20-epi-1,25dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin;acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists;altretamine; ambamustine; amidox; amifostine; aminolevulinic acid;amrubicin; amsacrine; anagrelide; anastrozole; andrographolide;angiogenesis inhibitors; antagonist D; antagonist G; antarelix;anti-dorsalizing morphogenetic protein-1; antiandrogen, prostaticcarcinoma; antiestrogen; antineoplaston; antisense oligonucleotides;aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators;apurinic acid; ara-CDP-DL-PTBA; arginine deaminase; asulacrine;atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3;azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol;batimastat; BCR/ABL antagonists; benzochlorins; benzoylstaurosporine;beta Lactam Derivatives; beta-alethine; betaclamycin B; betulinic acid;bFGF inhibitor; bicalutamide; bisantrene; bisaziridinylspermine;bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane;buthionine sulfoximine; calcipotriol; calphostin C; camptothecinderivatives; canarypox IL-2; carboxamide-amino-triazole;carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor;carzelesin; casein kinase inhibitors (ICOS); castanospermine; cecropinB; cetrorelix; chlorlns; chloroquinoxaline sulfonamide; cicaprost;cis-porphyrin; cladribine; clomifene Analogues; clotrimazole;collismycin A; collismycin B; combretastatin A4; combretastatinAnalogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8;cryptophycin A derivatives; curacin A; cyclopentanthraquinones;cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor;cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin;dexamethasone; dexifosfamide; dexrazoxane; dexverapamil; diaziquone;didemnin B; didox; diethylnorspermine; dihydro-5-acytidine;dihydrotaxol; dioxamycin; diphenyl spiromustine; docetaxel; docosanol;dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA;ebselen; ecomustine; edelfosine; edrecolomab; eflornithine; elemene;emitefur; epirubicin; epristeride; estramustine Analogue; estrogenagonists; estrogen antagonists; etanidazole; etoposide phosphate;exemestane; fadrozole; fazarabine; fenretinide; filgrastim; finasteride;flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicinhydrochloride; forfenimex; formestane; fostriecin; fotemustine;gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix;gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam;heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid;idarubicin; idoxifene; idramantone; ilmofosine; ilomastat;imidazoacridones; imiquimod; immunostimulant peptides; insulin-likegrowth factor-1 receptor inhibitor; interferon agonists; interferons;interleukins; iobenguane; iododoxorubicin; ipomeanol, 4-; iroplact;irsogladine; isobengazole; isohomohalicondrin B; itasetron;jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide;leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole;leukemia inhibiting factor; leukocyte alpha interferon;leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole;linear polyamine Analogue; lipophilic disaccharide peptide; lipophilicplatinum complexes; lissoclinamide 7; lobaplatin; lombricine;lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine;lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides;maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysininhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone;meterelin; methioninase; metoclopramide; MIF inhibitor; mifepristone;miltefosine; mirimostim; mismatched double stranded RNA; mitoguazone;mitolactol; mitomycin Analogues; mitonafide; mitotoxin fibroblast growthfactor-saporin; mitoxantrone; mofarotene; molgramostim; monoclonalantibody, human chorionic gonadotrophin; monophosphoryl lipidA+myobacterium cell wall sk; mopidamol; multiple drug resistance geneinhibitor; multiple tumor suppressor 1-based therapy; mustard anticanceragents; mycaperoxide B; mycobacterial cell wall extract; myriaporone;N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip;naloxone+pentazocine; napavin; naphterpin; nartograstim; nedaplatin;nemorubicin; neridronic acid; neutral endopeptidase; nilutamide;nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn;06-benzylguanine; octreotide; okicenone; oligonucleotides; onapristone;ondansetron; ondansetron; oracin; oral cytokine inducer; ormaplatin;osaterone; oxaliplatin; oxaunomycin; paclitaxel; paclitaxel Analogues;paclitaxel derivatives; palauamine; palmitoylrhizoxin; pamidronic acid;panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase;peldesine; pentosan polysulfate sodium; pentostatin; pentrozole;perflubron; perfosfamide; perillyl alcohol; phenazinomycin;phenylacetate; phosphatase inhibitors; picibanil; pilocarpinehydrochloride; pirarubicin; piritrexim; placetin A; placetin B;plasminogen activator inhibitor; platinum complex; platinum complexes;platinum-triamine complex; porfimer sodium; porfiromycin; prednisone;propyl bis-acridone; prostaglandin J2; proteasome inhibitors; proteinA-based immune modulator; protein kinase C inhibitor; protein kinase Cinhibitors, microalgal; protein tyrosine phosphatase inhibitors; purinenucleoside phosphorylase inhibitors; purpurins; pyrazoloacridine;pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists;raltitrexed; ramosetron; ras farnesyl protein transferase inhibitors;ras inhibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re186 etidronate; rhizoxin; ribozymes; RII retinamide; rogletimide;rohitukine; romurtide; roquinimex; rubiginone B1; ruboxyl; safingol;saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 mimetics;semustine; senescence derived inhibitor 1; sense oligonucleotides;signal transduction inhibitors; signal transduction modulators; singlechain antigen binding protein; sizofuran; sobuzoxane; sodiumborocaptate; sodium phenylacetate; solverol; somatomedin bindingprotein; sonermin; sparfosic acid; spicamycin D; spiromustine;splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem-celldivision inhibitors; stipiamide; stromelysin inhibitors; sulfinosine;superactive vasoactive intestinal peptide antagonist; suradista;suramin; swainsonine; synthetic glycosaminoglycans; tallimustine;tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium;tegafur; tellurapyrylium; telomerase inhibitors; temoporfin;temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine;thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic;thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroidstimulating hormone; tin ethyl etiopurpurin; tirapazamine; titanocenebichloride; topsentin; toremifene; totipotent stem cell factor;translation inhibitors; tretinoin; triacetyluridine; triciribine;trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinaseinhibitors; tyrphostins; UBC inhibitors; ubenimex; urogenitalsinus-derived growth inhibitory factor; urokinase receptor antagonists;vapreotide; variolin B; vector system, erythrocyte gene therapy;velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaltine;vitaxin; vorozole; zanoterone; zeniplatin; zilascorb; and zinostatinstimalamer.

In one another embodiment, the other anticancer agent is interferon-α.

In another embodiment, the other anticancer agent is interleukin-2.

In one embodiment, the other anticancer agent is an alkylating agent,such as a nitrogen mustard, a nitrosourea, an alkylsulfonate, atriazene, or a platinum-containing agent.

In one embodiment, the other anticancer agent is a triazene alkylatingagent.

In another embodiment, the other anticancer agent is temozolomide,procarbazine, dacarbazine, interleukin-2, irinotecan, doxorubicin, or acombination thereof.

In a specific embodiment, the other anticancer agent is temozolomide.

Temozolomide can be administered to a subject at dosages ranging fromabout 60 mg/m² (of a subject's body surface area) to about 250 mg/m² andfrom about 100 mg/m² to about 200 mg/m². In specific embodiments, thedosages of temozolomide are about 10 mg/m², about 1 mg/m², about 5mg/m², about 10 mg/m², about 20 mg/m², about 30 mg/m², about 40 mg/m²,about 50 mg/m², about 60 mg/m², about 70 mg/m², about 80 mg/m², about 90mg/m², about 100 mg/m², about 110 mg/m², about 120 mg/m², about 130mg/m², about 140 mg/m², about 150 mg/m², about 160 mg/m², about 170mg/m², about 180 mg/m², about 190 mg/m², about 200 mg/m², about 210mg/m², about 220 mg/m², about 230 mg/m², about 240 mg/m², or about 250mg/m².

In a specific embodiment, temozolomide is administered orally.

In one embodiment, temozolomide is administered orally to a subject at adose ranging from about 150 mg/m² to about 200 mg/m².

In another embodiment, temozolomide is administered orally to a subjectonce per day for five consecutive days at a dose ranging from about 150mg/m² to about 200 mg/m².

In a specific embodiment, temozolomide is administered orally to asubject once per day for five consecutive days at a dose ranging fromabout 150 mg/m² to about 200 mg/m² on days 1-5, then again orally onceper day for five consecutive days on days 28-32 at a dose ranging fromabout 150 mg/m² to about 200 mg/m², then again orally once per day forfive consecutive days on days 55-59 at a dose ranging from about 150mg/m² to about 200 mg/m².

In another embodiment, temozolomide is administered orally to a subjectonce per day for a week, two weeks, three weeks, a month or longer atthe foregoing daily dosage.

In a specific embodiment, the other anticancer agent is procarbazine.

Procarbazine can be administered to a subject at dosages ranging fromabout 50 mg/m² (of a subject's body surface area) to about 100 mg/m² andfrom about 60 mg/m² to about 100 mg/m². In specific embodiments, thedosages of procarbazine are about 10 mg/m², about 1 mg/m², about 5mg/m², about 10 mg/m², about 20 mg/m², about 30 mg/m², about 40 mg/m²,about 50 mg/m², about 60 mg/m², about 70 mg/m², about 80 mg/m², about 90mg/m², about 100 mg/m², about 110 mg/m², about 120 mg/m², about 130mg/m², about 140 mg/m², about 150 mg/m², about 160 mg/m², about 170mg/m², about 180 mg/m², about 190 mg/m², about 200 mg/m², about 210mg/m², about 220 mg/m², about 230 mg/m², about 240 mg/m², about 250mg/m², about 260 mg/m², about 270 mg/m², about 280 mg/m², about 290mg/m², about 300 mg/m², about 310 mg/m², about 320 mg/m², about 330mg/m², about 340 mg/m², about 350 mg/m², about 360 mg/m², about 370mg/m², about 380 mg/m², about 390 mg/m², about 400 mg/m², about 410mg/m², about 420 mg/m², about 430 mg/m², about 440 mg/m², about 450mg/m², about 460 mg/m², about 470 mg/m², about 480 mg/m², about 490mg/m², or about 500 mg/m².

In a specific embodiment, procarbazine is administered intravenously.

In one embodiment, procarbazine is administered intravenously to asubject at a dose ranging from about 50 mg/m² to about 100 mg/m².

In another embodiment, procarbazine is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 100 mg/m².

In a specific embodiment, procarbazine is administered intravenously toa subject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 100 mg/m² on days 1-5, then again intravenouslyonce per day for five consecutive days on days 28-32 at a dose rangingfrom about 50 mg/m² to about 100 mg/m², then again intravenously onceper day for five consecutive days on days 55-59 at a dose ranging fromabout 50 mg/m to about 100 mg/m².

In another embodiment, procarbazine is administered once intravenouslyto a subject at a dose ranging from about 50 mg/m² to about 100 mg/m².

In another embodiment, procarbazine is administered intravenously to asubject once per day for a week, two weeks, three weeks, a month orlonger at the foregoing daily dosage.

In a specific embodiment, the other anticancer agent is dacarbazine.

Dacarbazine can be administered to a subject at dosages ranging fromabout 60 mg/m² (of a subject's body surface area) to about 250 mg/m² andfrom about 150 mg/m² to about 250 mg/m². In specific embodiments, thedosages of dacarbazine are about 10 mg/m, about 1 mg/m², about 5 mg/m²,about 10 mg/m², about 20 mg/m², about 30 mg/m², about 40 mg/m², about 50mg/m², about 60 mg/m², about 70 mg/m², about 80 mg/m², about 90 mg/m²,about 100 mg/m², about 110 mg/m², about 120 mg/m², about 130 mg/m²,about 140 mg/m², about 150 mg/m², about 160 mg/m², about 170 mg/m²,about 180 mg/m², about 190 mg/m², about 200 mg/m², about 210 mg/m²,about 220 mg/m², about 230 mg/m², about 240 mg/m², about 250 mg/m²,about 260 mg/m², about 270 mg/m², about 280 mg/m², about 290 mg/m²,about 300 mg/m², about 310 mg/m², about 320 mg/m², about 330 mg/m²,about 340 mg/m², about 350 mg/m², about 360 mg/m², about 370 mg/m²,about 380 mg/m², about 390 mg/m², about 400 mg/m², about 410 mg/m²,about 420 mg/m², about 430 mg/m², about 440 mg/m², about 450 mg/m²,about 460 mg/m², about 470 mg/m², about 480 mg/m², about 490 mg/m², orabout 500 mg/m².

In a specific embodiment, dacarbazine is administered intravenously.

In one embodiment, dacarbazine is administered intravenously to asubject at a dose ranging from about 150 mg/m² to about 250 mg/m².

In another embodiment, dacarbazine is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 150 mg/m² to about 250 mg/m².

In a specific embodiment, dacarbazine is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 150 mg/m² to about 250 mg/m² on days 1-5, then again intravenouslyonce per day for five consecutive days on days 28-32 at a dose rangingfrom about 150 mg/m² to about 250 mg/m², then again intravenously onceper day for five consecutive days on days 55-59 at a dose ranging fromabout 150 mg/m² to about 250 mg/m².

In one embodiment, dacarbazine is administered once intravenously to asubject at a dose ranging from about 150 mg/m² to about 250 mg/m².

In another embodiment, dacarbazine is administered intravenously to asubject once per day for a week, two weeks, three weeks, a month orlonger at the foregoing daily dosage.

In a specific embodiment, the other anticancer agent is doxorubicin.

Doxorubicin can be administered to a subject at dosages ranging fromabout 50 mg/m² (of a subject's body surface area) to about 100 mg/m² andfrom about 60 mg/m² to about 100 mg/m². In specific embodiments, thedosages of doxorubicin are about 10 mg/m², about 1 mg/m², about 5 mg/m²,about 10 mg/m², about 20 mg/m², about 30 mg/m², about 40 mg/m², about 50mg/m², about 60 mg/m², about 70 mg/m², about 80 mg/m², about 90 mg/m²,about 100 mg/m², about 110 mg/m², about 120 mg/m², about 130 mg/m²,about 140 mg/m², about 150 mg/m², about 160 mg/m², about 170 mg/m²,about 180 mg/m², about 190 mg/m², about 200 mg/m², about 210 mg/m²,about 220 mg/m², about 230 mg/m², about 240 mg/m², about 250 mg/m²,about 260 mg/m², about 270 mg/m², about 280 mg/m², about 290 mg/m²,about 300 mg/m², about 310 mg/m², about 320 mg/m², about 330 mg/m²,about 340 mg/m², about 350 mg/m², about 360 mg/m², about 370 mg/m²,about 380 mg/m², about 390 mg/m², about 400 mg/m², about 410 mg/m²,about 420 mg/m², about 430 mg/m², about 440 mg/m², about 450 mg/m²,about 460 mg/m², about 470 mg/m², about 480 mg/m², about 490 mg/m², orabout 500 mg/m².

In a specific embodiment, doxorubicin is administered intravenously.

In one embodiment, doxorubicin is administered intravenously to asubject at a dose ranging from about 50 mg/m² to about 100 mg/m².

In another embodiment, doxorubicin is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 100 mg/m².

In a specific embodiment, doxorubicin is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 100 mg/m² on days 1-5, then again intravenouslyonce per day for five consecutive days on days 28-32 at a dose rangingfrom about 50 mg/m² to about 100 mg/m², then again intravenously onceper day for five consecutive days on days 55-59 at a dose ranging fromabout 50 mg/m² to about 100 mg/m².

In another embodiment, doxorubicin is administered once intravenously toa subject at a dose ranging from about 50 mg/m² to about 100 mg/m².

In another embodiment, doxorubicin is administered intravenously to asubject once per day for a week, two weeks, three weeks, a month orlonger at the foregoing daily dosage.

In one embodiment, the other anticancer agent is a Topoisomerase Iinhibitor, such as etoposide, teniposide, topotecan, irinotecan,9-aminocamptothecin, camptothecin, or crisnatol.

In a specific embodiment, the other anticancer agent is irinotecan.

Irinotecan can be administered to a subject at dosages ranging fromabout 50 mg/m² (of a subject's body surface area) to about 150 mg/m² andfrom about 75 mg/m² to about 150 mg/m². In specific embodiments, thedosages of irinotecan are about 10 mg/m², about 1 mg/m², about 5 mg/m²,about 10 mg/m², about 20 mg/m², about 30 mg/m², about 40 mg/m², about 50mg/m², about 60 mg/m², about 70 mg/m², about 80 mg/m², about 90 mg/m²,about 100 mg/m², about 110 mg/m², about 120 mg/m², about 130 mg/m²,about 140 mg/m², about 150 mg/m², about 160 mg/m², about 170 mg/m²,about 180 mg/m², about 190 mg/m², about 200 mg/m², about 210 mg/m²,about 220 mg/m², about 230 mg/m², about 240 mg/m², about 250 mg/m²,about 260 mg/m², about 270 mg/m², about 280 mg/m², about 290 mg/m²,about 300 mg/m², about 310 mg/m², about 320 mg/m², about 330 mg/m²,about 340 mg/m², about 350 mg/m², about 360 mg/m², about 370 mg/m²,about 380 mg/m², about 390 mg/m², about 400 mg/m², about 410 mg/m²,about 420 mg/m², about 430 mg/m², about 440 mg/m², about 450 mg/m²,about 460 mg/m², about 470 mg/m², about 480 mg/m², about 490 mg/m², orabout 500 mg/m².

In a specific embodiment, irinotecan is administered intravenously.

In one embodiment, irinotecan is administered intravenously to a subjectat a dose ranging from about 50 mg/m² to about 150 mg/m².

In another embodiment, irinotecan is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 150 mg/m².

In a specific embodiment, irinotecan is administered intravenously to asubject once per day for five consecutive days at a dose ranging fromabout 50 mg/m² to about 150 mg/m² on days 1-5, then again intravenouslyonce per day for five consecutive days on days 28-32 at a dose rangingfrom about 50 mg/m² to about 150 mg/m², then again intravenously onceper day for five consecutive days on days 55-59 at a dose ranging fromabout 50 mg/m² to about 150 mg/m².

In another embodiment, irinotecan is administered intravenously to asubject once per day for a week, two weeks, three weeks, a month orlonger at the foregoing daily dosage.

In one embodiment, the other anticancer agent is O-6-benzylguanine.

In another embodiment, the other anticancer agent is O-6-benzylguanineand temozolomide.

In another embodiment, the other anticancer agent is O-6-benzylguanineand procarbazine.

In still another embodiment, the other anticancer agent isO-6-benzylguanine and dacarbazine.

5.8.10.3 Multi-Therapy for Cancer

The Indenoisoquinolinone Analogs can be administered to a subject thathas undergone or is currently undergoing one or more additionalanticancer therapies including, but not limited to, surgery, radiationtherapy, or immunotherapy, such as cancer vaccines.

In one embodiment, the invention provides methods for treating orpreventing cancer comprising administering to a subject in need thereofan effective amount of an Indenoisoquinolinone Analog to treat orprevent cancer and another anticancer therapy including, but not limitedto, surgery, radiation therapy, or immunotherapy, such as a cancervaccine.

In one embodiment, the other anticancer therapy is radiation therapy.

In another embodiment, the other anticancer therapy is surgery.

In still another embodiment, the other anticancer therapy isimmunotherapy.

In a specific embodiment, the present methods for treating or preventingcancer comprise administering an effective amount of anIndenoisoquinolinone Analog and radiation therapy. The radiation therapycan be administered concurrently with, prior to, or subsequent to theIndenoisoquinolinone Analog, in one embodiment at least an hour, fivehours, 12 hours, a day, a week, a month, in another embodiment severalmonths (e.g., up to three months), prior or subsequent to administrationof the Indenoisoquinolinone Analog.

Where the other anticancer therapy is radiation therapy, any radiationtherapy protocol can be administered depending upon the type of cancerto be treated. For example, but not by way of limitation, X-rayradiation can be administered; specifically, high-energy megavoltage(radiation of greater that 1 MeV energy) can be administered for deeptumors, and electron beam and orthovoltage X-ray radiation can beadministered for skin cancers. Gamma-ray emitting radioisotopes, such asradioactive isotopes of radium, cobalt and other elements, can also beadministered.

Additionally, the invention provides methods of treatment of cancercomprising administering an Indenoisoquinolinone Analog as analternative to chemotherapy or radiation therapy where the chemotherapyor the radiation therapy results in a negative side effect in thesubject being treated. The subject being treated can, optionally, betreated with another anticancer therapy such as surgery, radiationtherapy, or immunotherapy.

The Indenoisoquinolinone Analogs can also be administered in vitro or exvivo, such as for the treatment of certain cancers, including, but notlimited to leukemias and lymphomas, such treatment involving autologousstem cell transplants. This can involve a process in which the subject'sautologous hematopoietic stem cells are harvested and purged of allcancer cells, the subject's remaining bone-marrow cell population isthen eradicated via the administration of an Indenoisoquinolinone Analogand/or radiation, and the resultant stem cells are infused back into thesubject. Supportive care can be subsequently provided while bone marrowfunction is restored and the subject recovers.

5.8.11 Treatment or Prevention of Erectile Dysfunction

The Indenoisoquinolinone Analogs are useful for treating or preventingerectile dysfunction. Erectile dysfunction includes an inability toachieve or maintain a full erection, specifically that which issufficient to achieve or maintain sexual intercourse. The inability canbe a total inability, an inconsistent ability, or a tendency to maintainonly a brief erection. Erectile dysfunction includes idiopathic erectiledysfunction, as well as that which can result, for example, from trauma,including mechanical trauma, specifically that resulting from surgery,to the nerves (such as during prostatectomy); diabetes mellitus; acardiovascular disease, including atherosclerosis; radiation; or certaindrugs. The erectile dysfunction can also be age-related.

In one embodiment, the erectile dysfunction results from prostatesurgery.

In a further embodiment, the erectile dysfunction results from prostatenerve injury.

5.8.12 Treatment or Prevention of Urinary Incontinence

The Indenoisoquinolinone Analogs are also useful for treating orpreventing urinary incontinence. Urinary incontinence can result, forexample, from trauma, including mechanical trauma, specifically duringchildbirth or that resulting from surgery, to the nerves (such as duringprostatectomy or gynecological surgery); diabetes mellitus; acardiovascular disease, including atherosclerosis; radiation; or certaindrugs. The urinary incontinence can also be age-related.

In one embodiment, the subject in need of urinary incontinence treatmentor prevention is male.

In one embodiment, the subject in need of urinary incontinence treatmentor prevention is female.

5.8.13 Treatment or Prevention of a Complication of Prematurity

The Indenoisoquinolinone Analogs are also useful for treating orpreventing a complication of prematurity. Examples of complications ofprematurity include, but are not limited to, retinopathy,hyaline-membrane disease and necrotizing enterocolitis.

5.8.14 Treatment or Prevention of Cardiomyopathy

The Indenoisoquinolinone Analogs are also useful for treating orpreventing cardiomyopathy.

5.8.15 Treatment or Prevention of Retinopathy

The Indenoisoquinolinone Analogs are also useful for treating orpreventing retinopathy.

5.8.16 Treatment or Prevention of Nephropathy

The Indenoisoquinolinone Analogs are also useful for treating orpreventing nephropathy.

5.8.17 Treatment or Prevention of Neuropathy

The Indenoisoquinolinone Analogs are also useful for treating orpreventing neuropathy.

5.9 Therapeutic/Prophylactic Administration and Compositions of theInvention

Due to their activity, the Indenoisoquinolinone Analogs areadvantageously useful in veterinary and human medicine. As describedabove, the Indenoisoquinolinone Analogs are useful for treating orpreventing a Condition in a subject in need thereof.

The Indenoisoquinolinone Analogs can be administered in amounts that areeffective to treat or prevent a Condition in a subject in need thereof.

When administered to a subject, the Indenoisoquinolinone Analogs can beadministered as a component of a composition that comprises aphysiologically acceptable carrier or vehicle. The present compositions,which comprise an Indenoisoquinolinone Analog, can be administeredorally. The Indenoisoquinolinone Analogs can also be administered by anyother convenient route, for example, by infusion or bolus injection, byabsorption through epithelial or mucocutaneous linings (e.g., oral,rectal, or intestinal mucosa) and can be administered together withanother biologically active agent. Administration can be systemic orlocal. Various delivery systems are known, e.g., encapsulation inliposomes, microparticles, microcapsules and capsules.

Methods of administration include, but are not limited to, intradermal,intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal,epidural, oral, sublingual, intracerebral, intravaginal, transdermal,rectal, by inhalation, or topical, specifically to the ears, nose, eyes,or skin. In some instances, administration will result in the release ofan Indenoisoquinolinone Analog into the bloodstream.

In one embodiment, the Indenoisoquinolinone Analogs are administeredorally.

In other embodiments, it can be desirable to administer theIndenoisoquinolinone Analogs locally. This can be achieved, for example,and not by way of limitation, by local infusion during surgery, topicalapplication, e.g., in conjunction with a wound dressing after surgery,by injection, by means of a catheter, by means of a suppository orenema, or by means of an implant, said implant being of a porous,non-porous, or gelatinous material, including membranes, such assialastic membranes, or fibers.

In certain embodiments, it can be desirable to introduce theIndenoisoquinolinone Analogs into the central nervous system orgastrointestinal tract by any suitable route, includingintraventricular, intrathecal, and epidural injection, and enema.Intraventricular injection can be facilitated by an intraventricularcatheter, for example, attached to a reservoir, such as an Ommayareservoir.

Pulmonary administration can also be employed, e.g., by use of aninhaler of nebulizer, and formulation with an aerosolizing agent, or viaperfusion in a fluorocarbon oar, synthetic pulmonary surfactant. Incertain embodiments, the Indenoisoquinolinone Analogs can be formulatedas a suppository, with traditional binders and excipients such astriglycerides.

In another embodiment Indenoisoquinolinone Analogs can be delivered in avesicle, specifically a liposome (see Langer, Science 249:1527-1533(1990) and Treat or prevent et al., Liposomes in Therapy of InfectiousDisease and Cancer 317-327 and 353-365 (1989)).

In yet another embodiment, the Indenoisoquinolinone Analogs can bedelivered in a controlled-release system or sustained-release system(see, e.g., Goodson, in Medical Applications of Controlled Release,supra, vol. 2, pp. 115-138 (1984)). Other controlled orsustained-release systems discussed in the review by Langer, Science249:1527-1533 (1990) can be used. In one embodiment a pump can be used(Langer, Science 249:1527-1533 (1990); Sefton, CRC Crit. Ref. Biomed.Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); and Saudeket al., N. Engl. J. Med. 321:574 (1989)). In another embodimentpolymeric materials can be used (see Medical Applications of ControlledRelease (Langer and Wise eds., 1974); Controlled Drug Bioavailability,Drug Product Design and Performance (Smolen and Ball eds., 1984); Rangerand Peppas, J. Macromol. Sci. Rev. Macromol. Chem. 2:61 (1983); Levy etal., Science 228:190 (1935); During et al., Ann. Neural. 25:351 (1989);and Howard et al., J. Neurosurg. 71:105 (1989)).

In yet another embodiment a controlled- or sustained-release system canbe placed in proximity of a target of the Indenoisoquinolinone Analogs,e.g., the spinal column, brain, skin, lung, or gastrointestinal tract,thus requiring only a fraction of the systemic dose.

The present compositions can optionally comprise a suitable amount of apharmaceutically acceptable excipient so as to provide the form forproper administration to the subject.

Such pharmaceutical excipients can be liquids, such as water and oils,including those of petroleum, animal, vegetable, or synthetic origin,such as peanut oil, soybean oil, mineral oil, sesame oil and the like.The pharmaceutical excipients can be saline, gum acacia, gelatin, starchpaste, talc, keratin, colloidal silica, urea and the like. In addition,auxiliary, stabilizing, thickening, lubricating, and coloring agents canbe used. In one embodiment, the pharmaceutically acceptable excipientsare sterile when administered to a subject. Water is a useful excipientwhen the Indenoisoquinolinone Analog is administered intravenously.Saline solutions and aqueous dextrose and glycerol solutions can also beemployed as liquid excipients, specifically for injectable solutions.Suitable pharmaceutical excipients also include starch, glucose,lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodiumstearate, glycerol monostearate, talc, sodium chloride, dried skim milk,glycerol, propylene, glycol, water, ethanol and the like. The presentcompositions, if desired, can also contain minor amounts of wetting oremulsifying agents, or pH buffering agents.

The present compositions can take the form of solutions, suspensions,emulsion, tablets, pills, pellets, capsules, capsules containingliquids, powders, sustained-release formulations, suppositories,emulsions. aerosols, sprays, suspensions, or any other form suitable foruse. In one embodiment, the composition is in the form of a capsule (seee.g. U.S. Pat. No. 5,698,155). Other examples of suitable pharmaceuticalexcipients are described in Remington's Pharmaceutical Sciences1447-1676 (Alfonso R. Gennaro eds., 19th ed. 1995), incorporated hereinby reference.

In one embodiment, the Indenoisoquinolinone Analog is formulated inaccordance with routine procedures as a composition adapted for oraladministration to human beings. Compositions for oral delivery can be inthe form of tablets, lozenges, aqueous or oily suspensions, granules,powders, emulsions, capsules, syrups, or elixirs for example. Orallyadministered compositions can contain one or more agents, for example,sweetening agents such as fructose, aspartame or saccharin; flavoringagents such as peppermint, oil of wintergreen, or cherry; coloringagents; and preserving agents, to provide a pharmaceutically palatablepreparation. Moreover, where in tablet or pill form, the compositionscan be coated to delay disintegration and absorption in thegastrointestinal tract thereby providing a sustained action over anextended period of time. Selectively permeable membranes surrounding anosmotically active driving an Indenoisoquinolinone Analog are alsosuitable for orally administered compositions. In these latterplatforms, fluid from the environment surrounding the capsule is imbibedby the driving compound, which swells to displace the agent or agentcomposition through an aperture. These delivery platforms can provide anessentially zero order delivery profile as opposed to the spikedprofiles of immediate release formulations. A time-delay material suchas glycerol monostearate or glycerol stearate can also be useful. Oralcompositions can include standard excipients such as mannitol, lactose,starch, magnesium stearate, sodium saccharin, cellulose, and magnesiumcarbonate. In one embodiment, the excipients are of pharmaceuticalgrade.

In another embodiment, the Indenoisoquinolinone Analogs can beformulated for intravenous administration. Typically, compositions forintravenous administration comprise sterile isotonic aqueous buffer.Where necessary, the compositions can also include a solubilizing agent.Compositions for intravenous administration can optionally include alocal anesthetic such as lignocaine to lessen pain at the site of theinjection. Generally, the ingredients are supplied either separately ormixed together in unit dosage form, for example, as a drylyophilized-powder or water-free concentrate in a hermetically sealedcontainer such as an ampule or sachette indicating the quantity ofactive agent. Where the Indenoisoquinolinone Analogs are to beadministered by infusion, they can be dispensed, for example, with aninfusion bottle containing sterile pharmaceutical grade water or saline.Where the Indenoisoquinolinone Analogs are administered by injection, anampule of sterile water for injection or saline can be provided so thatthe ingredients can be mixed prior to administration.

Indenoisoquinolinone Analogs can be administered by controlled-releaseor sustained-release means or by delivery devices that are well known tothose of ordinary skill in the art. Examples include, but are notlimited to, those described in U.S. Pat. Nos. 3,845,770; 3,916,899;3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767;5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,556, each of whichis incorporated herein by reference in its entirety. Such dosage formscan be useful for providing controlled- or sustained-release of one ormore active ingredients using, for example, hydropropylmethyl cellulose,other polymer matrices, gels, permeable membranes, osmotic systems,multilayer coatings, microparticles, liposomes, microspheres, or acombination thereof to provide the desired release profile in varyingproportions. Suitable controlled- or sustained-release formulationsknown to those skilled in the art, including those described herein, canbe readily selected for use with the active ingredients of theinvention. The invention thus encompasses single unit dosage formssuitable for oral administration such as, but not limited to, tablets,capsules, gelcaps, and caplets that are adapted for controlled- orsustained-release.

In one embodiment a controlled- or sustained-release compositioncomprises a minimal amount of an Indenoisoquinolinone Analog to treat orprevent the Condition over a period of time. Advantages of controlled-or sustained-release compositions include extended activity of the drug,reduced dosage frequency, and increased subject compliance. In addition,controlled- or sustained-release compositions can favorably affect thetime of onset of action or other characteristics, such as blood levelsof the Indenoisoquinolinone Analog, and can thus reduce the occurrenceof adverse side effects.

Controlled- or sustained-release compositions can initially release anamount of an Indenoisoquinolinone Analog that promptly produces thedesired therapeutic or prophylactic effect, and gradually andcontinually release other amounts of the Indenoisoquinolinone Analog tomaintain this level of therapeutic or prophylactic effect over anextended period of time. To maintain a constant level of theIndenoisoquinolinone Analog in the body, the Indenoisoquinolinone Analogcan be released from the dosage form at a rate that will replace theamount of Indenoisoquinolinone Analog being metabolized and excretedfrom the body. Controlled- or sustained-release of an active ingredientcan be stimulated by various conditions, including but not limited to,changes in pH, changes in temperature, concentration or availability ofenzymes, concentration or availability of water, or other physiologicalconditions or compounds.

The amount of the Indenoisoquinolinone Analog that is effective in thetreatment or prevention of a Condition can be determined by standardclinical techniques. In addition, in vitro or in vivo assays canoptionally be employed to help identify optimal dosage ranges. Theprecise dose to be employed can also depend on the route ofadministration, and the seriousness of the condition being treated andcan be decided according to the judgment of the practitioner and eachsubject's circumstances in view of, e.g., published clinical studies.Suitable effective dosage amounts, however, range from about 10micrograms to about 5 grams about every 4 hours, although they aretypically about 500 mg or less per every 4 hours. In one embodiment, theeffective dosage is about 0.01 mg, 0.5 mg, about 1 mg, about 50 mg,about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg,about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1 g, about1.2 g, about 1.4 g, about 1.6 g, about 1.8 g, about 2.0 g, about 2.2 g,about 2.4 g, about 2.6 g, about 2.8 g, about 3.0 g, about 3.2 g, about3.4 g, about 3.6 g, about 3.8 g, about 4.0 g, about 4.2 g, about 4.4 g,about 4.6 g, about 4.8 g, and about 5.0 g, every 4 hours. Equivalentdosages can be administered over various time periods including, but notlimited to, about every 2 hours, about every 6 hours, about every 8hours, about every 12 hours, about every 24 hours, about every 36 hours,about every 48 hours, about every 72 hours, about every week, aboutevery two weeks, about every three weeks, about every month, and aboutevery two months. The effective dosage amounts described herein refer tototal amounts administered; that is, if more than oneIndenoisoquinolinone Analog is administered, the effective dosageamounts correspond to the total amount administered.

Compositions can be prepared according to conventional mixing,granulating or coating methods, respectively, and the presentcompositions can contain, in one embodiment, from about 0.1% to about99%; and in another embodiment from about 1% to about 70% of theIndenoisoquinolinone Analog by weight or volume.

The dosage regimen utilizing the Indenoisoquinolinone Analog can beselected in accordance with a variety of factors including type,species, age, weight, sex and medical condition of the subject; theseverity of the condition to be treated; the route of administration;the renal or hepatic function of the subject; and the specificIndenoisoquinolinone Analog employed. A person skilled in the art canreadily determine the effective amount of the drug useful for treatingor preventing the Condition.

An Indenoisoquinolinone Analog can be administered in a single dailydose, or the total daily dosage can be administered in divided doses oftwo, three or four times daily. Furthermore, an IndenoisoquinolinoneAnalog can be administered in intranasal form via topical use ofsuitable intranasal vehicles, or via transdermal routes, using thoseforms of transdermal skin patches well known to those of ordinary skillin that art. To be administered in the form of a transdermal deliverysystem, the dosage administration can be continuous rather thanintermittent throughout the dosage regimen. Other illustrative topicalpreparations include creams, ointments, lotions, aerosol sprays andgels, wherein the concentration of Indenoisoquinolinone Analog rangesfrom about 0.1% to about 15%, w/w or w/v.

The Indenoisoquinolinone Analogs can be assayed in vitro or in vivo forthe desired therapeutic or prophylactic activity prior to use in humans.Animal model systems can be used to demonstrate safety and efficacy.

The present methods for treating or preventing a Condition in a subjectin need thereof can further comprise administering another prophylacticor therapeutic agent to the subject being administered anIndenoisoquinolinone Analog. In one embodiment, the other prophylacticor therapeutic agent is administered in an effective amount. The otherprophylactic or therapeutic agent includes, but is not limited to, ananti-inflammatory agent, an anti-renal failure agent, an anti-diabeticagent, and anti-cardiovasculare disease agent, an antiemetic agent, ahematopoietic colony stimulating factor, an anxiolytic agent, and ananalgesic agent.

In one embodiment, the other prophylactic or therapeutic agent is anagent useful for reducing any potential side effect of anIndenoisoquinolinone Analog. Such potential side effects include, butare not limited to, nausea, vomiting, headache, low white blood cellcount, low red blood cell count, low platelet count, headache, fever,lethargy, a muscle ache, general pain, bone pain, pain at an injectionsite, diarrhea, neuropathy, pruritis, a mouth sore, alopecia, anxiety ordepression.

In one embodiment, the Indenoisoquinolinone Analog can be administeredprior to, concurrently with, or after an anti-inflammatory agent, or onthe same day, or within 1 hour, 2 hours, 12 hours, 24 hours, 48 hours or72 hours of each other.

In another embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after an anti-renal failureagent, or on the same day, or within 1 hour, 2 hours, 12 hours, 24hours, 48 hours or 72 hours of each other.

In still another embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after an anti-diabeticagent, or on the same day, or within 1 hour, 2 hours, 12 hours, 24hours, 48 hours or 72 hours of each other.

In yet another embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after ananti-cardiovascular disease agent, or on the same day, or within 1 hour,2 hours, 12 hours, 24 hours, 48 hours or 72 hours of each other.

In a further embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after an antiemetic agent,or on the same day, or within 1 hour, 2 hours, 12 hours, 24 hours, 48hours or 72 hours of each other.

In another embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after a hematopoieticcolony stimulating factor, or on the same day, or within 1 hour, 2hours, 12 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 3 weeksor 4 weeks of each other.

In still embodiment, the Indenoisoquinolinone Analog can be administeredprior to, concurrently with, or after an opioid or non-opioid analgesicagent, or on the same day, or within 1 hour, 2 hours, 12 hours, 24hours, 48 hours or 72 hours of each other.

In yet another embodiment, the Indenoisoquinolinone Analog can beadministered prior to, concurrently with, or after an anxiolytic agent,or on the same day, or within 1 hour, 2 hours, 12 hours, 24 hours, 48hours or 72 hours of each other.

Effective amounts of the other prophylactic or therapeutic agents arewell known to those skilled in the art. However, it is well within theskilled artisan's purview to determine the other prophylactic ortherapeutic agent's optimal effective amount range. In one embodiment ofthe invention, where another prophylactic or therapeutic agent isadministered to a subject, the effective amount of theIndenoisoquinolinone Analog is less than its effective amount would bewhere the other prophylactic or therapeutic agent is not administered.In this case, without being bound by theory, it is believed thatIndenoisoquinolinone Analogs and the other prophylactic or therapeuticagent act synergistically to treat or prevent a Condition.

In one embodiment, the other therapeutic or prophylactic agent is ananti-inflammatory agent. Anti-inflammatory agents useful in the methodsof the present invention include but are not limited toadrenocorticosteroids, such as cortisol, cortisone, fludrocortisone,prednisone, prednisolone, 6α-methylprednisolone, triamcinolone,betamethasone, and dexamethasone; and non-steroidal anti-inflammatoryagents (NSAIDs), such as aspirin, acetaminophen, indomethacin, sulindac,tolmetin, diclofenac, ketorolac, ibuprofen, naproxen, flurbiprofen,ketoprofen, fenoprofen, oxaprozin, mefenamic acid, meclofenamic acid,piroxicam, meloxicam, nabumetone, rofecoxib, celecoxib, etodolac, andnimesulide.

In one embodiment, the other therapeutic or prophylactic agent is ananti-renal failure agent. Anti-renal failure agents useful in themethods of the present invention include include but are not limited toACE (angiotensin-converting enzyme) inhibitors, such as captopril,enalaprilat, lisinopril, benazepril, fosinopril, trandolapril,quinapril, and ramipril; diuretics, such as mannitol, glycerin,furosemide, toresemide, tripamide, chlorothiazide, methyclothiazide,indapamide, amiloride, and spironolactone; and fibric acid agents, suchas clofibrate, gemfibrozil, fenofibrate, ciprofibrate, and bezafibrate.

In one embodiment, the other therapeutic or prophylactic agent is ananti-diabetic agent. Anti-diabetic agents useful in the methods of thepresent invention include include but are not limited to glucagons;somatostatin; diazoxide; sulfonylureas, such as tolbutamide,acetohexamide, tolazamide, chloropropamide, glybenclamide, glipizide,gliclazide, and glimepiride; insulin secretagogues, such as repaglinide,and nateglinide; biguanides, such as metformin and phenformin;thiazolidinediones, such as pioglitazone, rosiglitazone, andtroglitazone; and α-glucosidase inhibitors, such as acarbose andmiglitol.

In one embodiment, the other therapeutic or prophylactic agent is ananti-cardiovascular agent. Anti-cardiovascular disease agents useful inthe methods of the present invention include include but are not limitedto carnitine; thiamine; and muscarinic receptor antagonists, such asatropine, scopolamine, homatropine, tropicamide, pirenzipine,ipratropium, tiotropium, and tolterodine.

In one embodiment, the other therapeutic or prophylactic agent is anantiemetic agent. Antiemetic agents useful in the methods of the presentinvention include include, but are not limited to, metoclopromide,domperidone, prochlorperazine, promethazine, chlorpromazine,trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucinemonoethanolamine, alizapride, azasetron, benzquinamide, bietanautine,bromopride, buclizine, clebopride, cyclizine, dimenhydrinate,diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone,oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol,thiethylperazine, thioproperazine, tropisetron, and mixtures thereof.

In one embodiment, the other therapeutic or prophylactic agent is ahematopoietic colony stimulating factor. Hematopoietic colonystimulating factors useful in the methods of the present inventioninclude, but are not limited to, filgrastim, sargramostim, molgramostimand epoietin alfa.

In one embodiment, the other therapeutic or prophylactic agent is anopioid analgesic agent. Opioid analgesic agents useful in the methods ofthe present invention include, but are not limited to, morphine, heroin,hydromorphone, hydrocodone, oxymorphone, oxycodone, metopon,apomorphine, normorphine, etorphine, buprenorphine, meperidine,lopermide, anileridine, ethoheptazine, piminidine, betaprodine,diphenoxylate, fentanil, sufentanil, alfentanil, remifentanil,levorphanol, dextromethorphan, phenazocine, pentazocine, cyclazocine,methadone, isomethadone and propoxyphene.

In one embodiment, the other therapeutic or prophylactic agent is anon-opioid analgesic agent. Non-opioid analgesic agents useful in themethods of the present invention include, but are not limited to,aspirin, celecoxib, rofecoxib, diclofinac, diflusinal, etodolac,fenoprofen, flurbiprofen, ibuprofen, ketoprofen, indomethacin,ketorolac, meclofenamate, mefanamic acid, nabumetone, naproxen,piroxicam and sulindac.

In one embodiment, the other therapeutic or prophylactic agent is ananxiolytic agent. Anxiolytic agents useful in the methods of the presentinvention include, but are not limited to, buspirone, andbenzodiazepines such as diazepam, lorazepam, oxazapam, chlorazepate,clonazepam, chlordiazepoxide and alprazolam.

5.10 Kits

The invention encompasses kits that can simplify the administration ofan Indenoisoquinolinone Analog to a subject.

A typical kit of the invention comprises a unit dosage form of anIndenoisoquinolinone Analog. In one embodiment, the unit dosage form isa container, which can be sterile, containing an effective amount of anIndenoisoquinolinone Analog and a physiologically acceptable carrier orvehicle. The kit can further comprise a label or printed instructionsinstructing the use of the Indenoisoquinolinone Analog to treat orprevent a Condition. The kit can also further comprise a unit dosageform of another prophylactic or therapeutic agent, for example, acontainer containing an effective amount of the other prophylactic ortherapeutic agent. In one embodiment, the kit comprises a containercontaining an effective amount of an Indenoisoquinolinone Analog and aneffective amount of another prophylactic or therapeutic agent. Examplesof other prophylactic or therapeutic agents include, but are not limitedto, those listed above.

The invention is further described in the following examples, which donot limit the scope of the invention described in the claims.

6. EXAMPLES Example 1 Illustrative Indenoisoquinolinone Analogs

General Methods:

¹H-NMR spectra were obtained using Varian 300 MHz spectrophotometer andchemical shifts (6) are reported in parts per million (ppm). ¹H-NMRspectra were obtained using DMSO-d₆ or CDCl₃ as solvents. Analyticalthin layer chromatography (TLC) was performed using TLC platespre-coated with silica gel 60 F-254. Compounds were visualized withshort wavelength UV light. All final compounds were characterized on thebasis of ¹H-NMR or mass-spectrometry (MS) data. Homophthalic anhydride,2-methyl-3-bromobenzoic acid, benzonitrile, and 3-methyl-4-bromobenzoicacid were obtained commercially (Sigma-Aldrich Corp., St. Louis, Mo.).

A. Synthesis of Indenoisocquinolinone Analogs of Formula Ia and IIIaMethyl 3-bromo-2-methylbenzoate

2 mL of concentrated sulfuric acid were added to a solution of3-bromo-2-methylbenzoic acid (20 g, 93 mmol) in methanol (150 mL). Theresultant mixture was refluxed for 6 hours. Methanol was removed underreduced pressure, and the residue was dissolved in a mixture ofchloroform (100 mL) and saturated solution of Na₂CO₃ (100 mL). Theorganic layer was separated and washed with brine, dried over Na₂SO₄ andconcentrated to provide methyl 3-bromo-2-methylbenzoate (21.1 g). ¹H NMRspectrum (in DMSO-d₆): δ 7.79 (d, J=8.0 Hz, 1H); 7.69 (d, J=7.9 Hz, 1H);7.23 (t, 1H); 3.82 (s, 3H).

Methyl 3-cyano-2-methylbenzoate

To a flask was added methyl 3-bromo-2-methylbenzoate (21 g, 91.7 mmol),potassium hexacyanoferrate (II) trihydrate (9.7 g, 22.9 mmol), Na₂CO₃(9.7 g, 91.7 mmol) and Pd(OAc)₂ (102 mg) in N,N-dimethylacetamide (100mL). The flask's atmosphere was evacuated and replaced with nitrogen,and the reaction mixture heated at 120° C. for 10 hours. The reactionmixture was cooled to room temperature and diluted with ethyl acetate(150 mL). The resultant slurry was filtered and washed thoroughly withethyl acetate (2×50 mL). The combined filtrate was washed with brine andwater, dried over Na₂SO₄ and evaporated under reduced pressure. Theresidue obtained after the concentration was purified using flashchromatography (ethyl acetate-hexanes (1:9) as the eluent) to providemethyl 3-cyano-2-methylbenzoate (11.2 g, 70% yield). ¹H NMR spectrum (inDMSO-d₆): δ 8.03 (d, J=8.1 Hz, 1H); 7.98 (d, J=7.9 Hz, 1H); 7.49 (t,1H); 3.84 (s, 3H); 2.65 (s, 3H).

Methyl 2-bromomethyl-3-cyanobenzoate

A suspension of methyl 3-cyano-2-methylbenzoate (10.6 g, 60.5 mmol), NBS(16.2 g, 90.7 mmol) and azobisisobutyronitrile (AIBN) (100 mg) intetrachloromethane (200 mL) was refluxed under nitrogen atmosphere for 6hours. TLC analysis indicated the complete consumption of methyl3-cyano-2-methylbenzoate (TLC solvent: 10% ethyl acetate in hexane). Thereaction mixture was filtered and washed with chloroform (3×20 mL). Thecombined filtrate and washings were concentrated under reduced pressure.The residue was washed through a short column of silica gel using 10%ethyl acetate in hexanes as an eluent. The eluent was concentrated andthe resultant product dried under vacuum overnight to provide 15.1 g ofmethyl 2-bromomethyl-3-cyanobenzoate (98% yield). ¹H NMR spectrum (inDMSO-d₆): δ 8.15 (d, J=8.0 Hz, 1H); 8.12 (d, J=7.9 Hz, 1H); 7.67 (t,1H); 5.04 (s, 2H); 3.89 (s, 3H).

Methyl 5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylate

A mixture of methyl 2-bromomethyl-3-cyanobenzoate (14.1 g, 55.5 mmol)and homophthalic anhydride (22.5 g, 138.8 mmol) in acetonitrile (150 mL)was stirred at room temperature. A solution of triethylamine (23.2 mL)in acetonitrile (100 mL) was added dropwise over the period of 1 hour.After the completion of addition, the resultant suspension was refluxedfor 4 hours. The reaction mixture was then cooled to room temperatureand filtered. The resultant solid was washed thoroughly withacetonitrile (100 mL) and ethanol (2×100 mL) and dried in vacuum oven at50° C. to provide methyl5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylate wasobtained in 81% yield (13.1 g). ¹H NMR spectrum (in DMSO-d₆): δ 12.21(s, 1H); 8.20 (m, 2H); 7.83 (d, J=7.5 Hz, 1H); 7.71 (m, 2H); 7.47 (m,2H); 4.07 (s, 2H); 3.89 (s, 3H).

10-Hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline

Fine powder of methyl5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylate (11.3 g,28.8 mmol) was suspended in THF (150 mL) and stirred at roomtemperature. A 2M solution of Lithium aluminium hydride (LAH) in THF (39mL) was added slowly to the stirred suspension. After the completeaddition, the mixture was stirred at room temperature for 6 hours, thencooled to 0° C. The reaction mixture was quenched with dropwise additionof ethyl acetate (50 mL). During the quenching the reaction temperaturewas kept below 50° C. The reaction mixture was poured into 1N HClsolution (200 mL) and stirred for 1 hour. The resultant solid wascollected by filtration, washed with 1N HCl solution (20 mL) and ethylacetate, and dried in a vacuum oven overnight to provide10-hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline in 93%yield (9.5 g). ¹H NMR spectrum (in DMSO-d₆): δ 12.28 (s, 1H); 8.23 (d,J=8.1 Hz, 1H); 7.89 (m, 1H); 7.73 (m, 2H); 7.45 (m, 1H); 7.36 (m, 2H);5.22 (d, J=5.1 Hz, 1H), 4.68 (d, 2H); 3.85 (s, 2H).

10-Bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline

Fine powder of10-hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline (7.3g, 27.7 mmol) was suspended in THF (150 mL). A solution of PBr₃ (83 mL,IM in dichloromethane) was added dropwise at room temperature. After thecomplete addition, the resultant mixture was stirred overnight andquenched by addition of water (150 mL). The suspension was stirred for 1hour and filtered. The resultant solid was washed with water (2×100 mL)and ethyl acetate (2×100 mL) and dried in a vacuum oven to provide110-Bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline in 81%yield. ¹H NMR spectrum (in DMSO-d₆): δ 12.31 (s, 1H); 8.23 d, J=7.5 Hz,1H); 7.95 (m, 1H); 7.75 (m, 2H); 7.45 (m, 2H); 4.87 (s, 2H); 3.97 (s,2H).

General Procedure for the Amination Reaction:

A suspension of10-bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline (0.425g, 1.3 mmol) or a higher alkylene chain bromo-derivative, an appropriateamine in ethanol or DMF and ethanol and in the presence of base isrefluxed for 2 hrs to overnight. The reaction mixture is stirred at roomtemperature for about 30 minutes and filtered. The resultant solid iswashed with ethanol (2×20 mL) and dried in a vacuum oven to provide anIndenoisoquinolinone Analog of Formula IIa or IIIa.

Methanesulfonate or Hydrochloride Salt Formation:

Free base of an Indenoisoquinolinone Analog of Formula IIb or IIIb issuspended in ethanol. To the stirred suspension, methanesulfonic acid orhydrochloric acid is added (2 to 10 equivalents). After some time, theresultant salt starts to precipitate from the solution. The mixture isstirred at room temperature for about 2 hours, filtered and washed withethanol (2×20 mL). The filtered solid is dissolved in water (10 mL) andfiltered. The filtrate is lyophilized to provide the corresponding saltof the free base of the Indenoisoquinolinone Analog of Formula Ia orIIIa.

B. Synthesis of Indenoisoquinolinone Analogs of Formula IIb and IIIbMethyl 4-cyano-3-methylbenzoate

Methyl 4-cyano-3-methylbenzoate was obtained in 86% yield according tothe procedure used to prepare methyl 3-cyano-2-methylbenzoate, exceptthat methyl 4-bromo-3-methylbenzoate was used in place of methyl3-bromo-2-methylbenzoate. ¹H NMR spectrum (in DMSO-d₆): δ 7.96 (s, 1H);7.85 (m, 2H); 3.85 (s, 3H); 2.46 (s, 3H).

Methyl 3-bromomethyl-4-cyanobenzoate

Methyl 3-bromomethyl-4-cyanobenzoate was obtained in 60% yield accordingto the procedure used to prepare methyl 2-bromomethyl-3-cyanobenzoate(supra), except that methyl 4-cyano-3-methylbenzoate was used in placeof methyl 3-cyano-2-methylbenzoate. ¹H NMR spectrum (in DMSO-d₆): δ 8.26(s, 1H); 8.02 (s, 2H); 4.89 (s, 2H); 3.88 (s, 3H).

Methyl 5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-9-carboxylate

Methyl 5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-9-carboxylatewas obtained in 65% yield according to the procedure used to preparemethyl 5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylate,except that methyl 3-bromomethyl-4-cyanobenzoate was used in place ofmethyl 2-bromomethyl-3-cyanobenzoate. ¹H NMR spectrum (in DMSO-d₆): δ12.35 (s, 1H); 8.25 (d, J=8.1 Hz, 1H); 8.11 (s, 1H); 8.06 (d, J=7.8 Hz,1H); 7.98 (d, J=8.1 Hz, 1H); 7.75 (m, 2H); 7.49 (m, 1H); 3.95 (s, 2H);3.85 (s, 3H).

9-Hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline

9-Hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline wasobtained in 96% yield according to the procedure used to prepare10-hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline,except that methyl5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-9-carboxylate was usedin place of methyl5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylate. ¹H NMRspectrum (in DMSO-d₆): δ 12.26 (s, 1H); 8.22 (d, J=8.1 Hz, 1H); 7.91 (s,J=8.1 Hz, 1H); 7.70 (m, 2H); 7.54 (s, 1H); 7.42 (m, 1H); 7.30 (d, J=8.1Hz, 1H); 5.21 (d, 1H); 4.55 (d, J=5.4 Hz, 2H); 3.89 (s, 2H).

9-Bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline

9-Bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline wasobtained in 65% yield according to the procedure used to prepare10-bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline, exceptthat 9-hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinolinewas used in place of10-hydroxymethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline. ¹HNMR spectrum (in DMSO-d₆): δ 12.24 (s, 1H); 8.23 (d, J=7.5 Hz, 1H); 7.94(d, J=7.8 Hz, 1H); 7.72 (m, 2H); 7.65 (s, 1H); 7.45 (m, 2H); 4.79 (s,2H); 3.89 (s, 2H).

General Procedure for the Amination Reaction:

A suspension of9-bromomethyl-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline (0.425 g,1.3 mmol) or a higher alkylene chain bromo-derivative, an appropriateamine in ethanol or DMF and ethanol and in the presence of base isrefluxed for 2 hrs to overnight. The reaction mixture is stirred at roomtemperature for about 30 minutes and filtered. The resultant solid iswashed with ethanol (2×20 mL) and dried in a vacuum oven to provide anIndenoisoquinolinone Analog of Formula IIb or IIIb.

Methanesulfonate or Hydrochloride Salt Formation:

Free base of an Indenoisoquinolinone Analog of Formula IIb or IIIb issuspended in ethanol. To the stirred suspension, methanesulfonic acid orhydrochloric acid is added (2 to 10 equivalents). After some time, theresultant salt starts to precipitate from the solution. The mixture isstirred at room temperature for about 2 hours, filtered and washed withethanol (2×20 mL). The filtered solid is dissolved in water (10 mL) andfiltered. The filtrate is lyophilized to provide the corresponding saltof the free base of the Indenoisoquinolinone Analog of Formula IIb orIIIb.

¹H NMR data for illustrative Indenoisoquinolinone Analogs are presentedbelow in Table 3.

TABLE 3 Compound ¹H NMR (DMSO-d₆ or DMSO-d₆ and D₂O) IIa-110-[1-(4-Allylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23 (d, J =8.1 Hz, 1H); 7.89 (d, J = 7.2 Hz, 1H); 7.75 (m, 2H); 7.45 (m, 1H); 7.37(t, J = 7.5 Hz, 1H); 7.28 (d, J = 7.5 Hz, 1H); 5.77 (m, 1H); 5.14 (d, J= 18.6 Hz, 1H); 5.08 (d, J = 10.8 Hz, 1H); 3.89 (s, 2H); 3.61 (s, 2H);2.89 (d, J = 6.0 Hz, 2H); 2.40 (m, 8H). MS: m/z = 372 (M⁺ − H) IIIa-210-[1-(4-Butylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.24 (d, J =7.8 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.74 (m, 2H); 7.45 (m, 1H); 7.36(t, J = 7.5 Hz, 1H); 7.27 (d, J = 7.2 Hz, 1H); 3.90 (s, 2H); 3.64 (s,2H); 2.38 (m, 10H); 1.41 (m, 2H); 1.24 (m, 2H); 0.85 (t, J = 7.2 Hz,3H). MS: m/z = 388 (M⁺ − H). Dihydrochloride10-[1-(4-Allylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H- salt of IIa-1indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO & D₂O) δ 12.35(s, 1H); 8.25 (d, J = 8.1 Hz, 1H); 8.04 (d, J = 7.5 Hz, 1H); 7.78 (t, J= 7.5 Hz, 1H); 7.72 (d, J = 7.5 Hz, 1H); 7.58 (s, 1H); 7.48 (m, 2H);5.94 (m, 1H); 5.56 (d, J = 19.2 Hz, 1H); 5.48 (d, J = 10.5 Hz, 1H); 4.15(s, 2H); 3.73 (s, 2H); 3.51 (m, 10H). Dihydrochloride10-[1-(4-Butylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H- salt of IIIa-2indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO & D₂O) δ 12.35(s, 1H); 8.25 (d, J = 8.1 Hz, 1H); 8.04 (d, J = 7.2 Hz, 1H); 7.78 (t, J= 7.2 Hz, 1H); 7.71 (d, J = 7.2 Hz, 1H); 7.58 (s, 1H); 7.48 (m, 2H);4.15 (s, 2H); 3.53 (m, 10H); 3.04 (s, 2H); 1.62 (m, 2H); 1.30 (m, 2H);0.88 (t, J = 7.2 Hz, 3H). MS: m/z = 388 (M⁺ − H). IIIa-310-[1-(4-Cyclopropylmethylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H);8.24 (d, J = 7.8 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.74 (m, 2H); 7.44(m, 1H); 7.35 (t, J = 7.5 Hz, 1H); 7.27 (d, J = 7.2 Hz, 1H); 3.88 (s,2H); 3.61 (s, 2H); 2.42 (m, 8H); 2.13 (d, J = 5.7 Hz, 2H); 0.78 (m, 2H);0.40 (d, J = 6.6 Hz, 2H); 0.02 (m, 2H). MS: m/z = 386 (M⁺ − H). IIa-1410-[(4,4-Ethylenedioxy-piperidino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO): δ 12.28 (s, 1H); 8.24(d, J = 7.8 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.76 (m, 2H); 7.45 (m,1H); 7.36 (t, J = 7.5 Hz, 1H); 7.29 (d, J = 7.2 Hz, 1H); 3.90 (s, 2H);3.84 (s, 4H); 3.64 (s, 2H); 2.45 (m, 4H); 1.61 (m, 4H). MS: m/z 389 (M⁺− H). IIIa-5 10-[N-(2-Pyrollidinoethyl)aminomethyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.23 (d,J = 8.1 Hz, 1H); 7.88 (dd, J = 2.1 Hz, 6.3 Hz, 1H); 7.74 (d, J = 3.6 Hz,2H); 7.44 (m, 1H); 7.34 (m, 2H); 3.89 (s, 2H); 3.87 (s, 2H); 2.62 (t, J= 6.3, 2H); 2.52 (m, 2H); 2.37 (m, 4H); 1.61 (m, 4H). MS: m/z 360 (M⁺ −H). IIa-27 10-{N-[1-(Hydroxymethyl)cyclopentyl]aminomethyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s,1H); 8.23 (d, J = 7.8 Hz, 1H); 7.86 (d, J = 6.9 Hz, 1H); 7.73 (m, 2H);7.45 (m, 1H); 7.36 (m, 2H); 4.56 (s, 1H); 3.90 (s, 2H); 3.79 (s, 2H);3.41 (s, 2H); 1.69 (m, 2H); 1.53 (m, 4H). MS: m/z = 361 (M⁺ − H). IIIa-610-{1-[4-(2-Pyrollidinoethyl)piperidino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.24 (s, 1H);8.24 (d, J = 7.8 Hz, 1H); 7.89 (d, J = 7.2 Hz, 1H); 7.75 (m, 2H); 7.45(m, 1H); 7.35 (t, J = 7.2 Hz, 1H); 7.28 (d, J = 7.2 Hz, 1H); 3.89 (s,2H); 3.58 (s, 2H); 2.79 (d, J = 9.9 Hz, 2H); 2.35 (m, 6H); 1.95 (t, J =10.6 Hz, 2H); 1.62 (m, 6H); 1.33 (m, 3H); 1.12 (m, 2H). MS: m/z = 428(M⁺ − H). IIIa-710-{N-[4-(1-Methylpiperidyl)]aminomethyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.23(d, J = 7.8 Hz, 1H); 7.87 (m, 1H); 7.75 (m, 2H); 7.46 (m, 1H); 7.36 (m,2H); 3.90 (s, 2H); 3.88 (s, 2H); 2.68 (d, J = 11.7 Hz, 2H); 2.40 (m,1H); 2.11 (s, 3H); 1.82 (m, 4H); 1.30 (m, 2H). IIIa-910-[1-(4-Cyclopentylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.24 (d,J = 7.8 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.74 (m, 2H); 7.44 (m, 1H);7.35 (t, J = 7.5 Hz, 1H); 7.28 (d, J = 7.2 Hz, 1H); 3.89 (s, 2H); 3.60(s, 2H); 2.41 (m, 9H); 1.71 (m, 2H); 1.56 (m, 2H); 1.45 (m, 2H); 1.28(m, 2H). MS: m/z = 400 (M⁺ − H). IIIa-810-{1-[4-(2-Pyrimidyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.32 (d,J = 4.8, 2H); 8.24 (d, J = 7.8 Hz, 1H); 7.92 (d, J = 6.8 Hz, 1H); 7.74(m, 2H); 7.44 (m, 1H); 7.35 (m, 2H); 6.59 (t, J = 4.8 Hz, 1H); 3.94 (s,2H); 3.73 (m, 4H); 3.68 (s, 2H); 2.46 (m, 4H). MS: m/z = 410 (M⁺ − H).IIIa-10 10-{1-[4-(2-Ethoxyethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23(d, J = 7.8 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.76 (m, 2H); 7.45 (m,1H); 7.35 (t, J = 7.5 Hz, 1H); 7.27 (d, J = 7.2 Hz, 1H); 3.89 (s, 2H);3.60 (s, 2H); 3.38 (m, 4H); 2.40 (m, 10H); 1.06 (t, J = 6.9 Hz, 3H). MS:m/z = 404 (M⁺ − H). IIb-19-[1-(4-Allylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.22 (d, J =7.8 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.51 (s, 1H); 7.44(m, 1H); 7.28 (d, J = 7.5 Hz, 1H); 5.76 (m, 1H); 5.13 (d, J = 18.9 Hz,1H); 5.08 (d, J = 11.2 Hz, 1H); 3.86 (s, 2H); 3.51 (s, 2H); 2.90 (d, J =6.0 Hz, 2H); 2.37 (m, 8H). MS: m/z = 372 (M⁺ − H). IIIb-19-[1-(4-iso-Propylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.22 (s, 1H); 8.23 (d, J =7.8 Hz, 1H); 7.92 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.50 (s, 1H); 7.43(m, 1H); 7.28 (d, J = 7.8 Hz, 1H); 3.86 (s, 2H); 3.50 (s, 2H); 2.60 (m,1H); 2.46-2.35 (m, 8H); 0.94 (d, J = 6.3 Hz, 6H). MS: m/z = 374 (M⁺ −H). IIIb-13 9-[1-(4-Methylhomopiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.24 (s, 1H); 8.23 (d,J = 8.1 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.53 (s, 1H);7.43 (m, 1H); 7.31 (d, J = 7.8 Hz, 1H); 3.86 (s, 2H); 3.65 (s, 2H);2.66-2.50 (m, 8H); 2.25 (s, 3H); 1.71 (m, 2H). m/z = 360 (M⁺ − H).Dihydrochloride9-[1-(4-Cyclopropylmethylpiperazino)methyl]-5,6-dihydro-5- salt ofIIIb-3 oxo-11-H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO& D₂O) δ 8.22 (d, J = 7.8 Hz, 1H); 7.98 (t, J = 7.5 Hz, 1H); 7.74 (m,3H); 7.50 (m, 2H); 4.35 (s, 2H); 3.87 (s, 2H); 3.38 (m, 8H); 3.04 (d, J= 6.3 Hz, 2H); 1.02 (m, 1H); 0.62 (d, J = 6.3 Hz, 2H); 0.34 (m, 2H). MS:m/z = 386 (M⁺ − H). Dihydrochloride9-[1-(4-iso-Propylpiperazino)methyl]-5,6-dihydro-5-oxo-11- salt ofIIIb-1 H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO) δ12.22 (s, 1H); 8.22 (d, J = 8.1 Hz, 1H); 7.99 (d, J = 7.8 Hz, 1H); 7.75(m, 3H); 7.56 (d, J = 7.8 Hz, 1H); 7.47 (m, 1H); 4.39 (s, 2H); 3.90 (s,2H); 3.54 (m, 9H); 1.23 (d, J = 6.0 Hz, 6H). MS: m/z = 374 (M⁺ − H).IIIb-2 9-[1-(4-Butylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.22 (d, J =8.1 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.50 (s, 1H); 7.43(m, 1H); 7.27 (d, J = 7.8 Hz, 1H); 3.86 (s, 2H); 3.50 (s, 2H); 2.35 (m,8H); 2.22 (t, J = 6.9 Hz, 2H); 1.37-1.20 (m, 4H); 0.84 (t, J = 6.9 Hz,3H). MS: m/z = 388 (M⁺ − H). Dihydrochloride9-[1-(4-Butylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H- salt of IIIb-2indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO) δ 12.23 (s,1H); 8.23 (d, J = 7.8 Hz, 1H); 8.00 (d, J = 8.1 Hz, 1H); 7.76 (m, 3H);7.55 (d, J = 7.5 Hz, 1H); 7.48 (m, 1H); 4.36 (s, 2H); 3.91 (s, 2H); 3.40(m, 8H); 3.09 (t, J = 7.5 Hz, 2H); 1.58 (m, 2H); 1.28 (m, 1H); 0.86 (t,J = 7.2 Hz, 3H). MS: m/z = 388 (M⁺ − H). Dihydrochloride9-[1-(4-Allylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H- salt of IIb-1indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO & D₂O) δ 8.22(d, J = 8.1 Hz, 1H); 7.97 (d, J = 7.8 Hz, 1H); 7.75 (m, 3H); 7.49 (m,2H); 5.83 (m, 1H); 5.53 (d, J = 19.5 Hz, 1H); 5.08 (d, J = 9.6 Hz, 1H);4.29 (s, 2H); 3.91 (s, 2H); 3.71 (d, J = 6.9 Hz, 2H); 3.32 (m, 8H).Dihydrochloride9-[1-(4-Cyclohexylpiperazino)methyl]-5,6-dihydro-5-oxo-11- salt ofIIIb-14 H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO & D₂O)δ 8.21 (d, J = 8.1 Hz, 1H); 7.94 (d, J = 7.8 Hz, 1H); 7.75 (d, J = 3.9Hz, 2H); 7.70 (s, 1H); 7.48 (m, 2H); 3.92 (s, 2H); 3.57 (s, 3H); 3.27(m, 8H); 2.05 (s, 2H); 1.79 (d, J = 10.8 Hz, 2H); 1.57 (d, J = 11.1 Hz,1H); 1.43-1.05 (m, 5H). IIIb-249-[1-(3,5-Dimethylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.22 (s, 1H); 8.22 (d, J =7.8 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.49 (s, 1H); 7.44(m, 1H); 7.28 (d, J = 7.8 Hz, 1H); 3.87 (s, 2H); 3.46 (s, 2H); 2.72 (m,2H); 2.65 (d, J = 9.3 Hz, 2H); 1.49 (t, J = 10.1 Hz, 3H); 0.87 (d, J =6.0 Hz, 6H). MS: m/z = 360 (M⁺ − H). IIIb-179-{1-[4-(2-Pyrollidinoethyl)piperidino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H);8.22 (d, J = 8.1 Hz, 1H); 7.91 (d, J = 7.5 Hz, 1H); 7.73 (m, 2H); 7.50(s, 1H); 7.44 (m, 1H); 7.28 (d, J = 7.8 Hz, 1H); 3.87 (s, 2H); 3.48 (s,2H); 2.79 (d, J = 11.1 Hz, 2H); 2.35 (m, 6H); 1.90 (t, J = 10.6 Hz, 2H);1.62 (m, 6H); 1.33 (m, 3H); 1.15 (m, 2H). MS: m/z = 428 (M⁺ − H). IIb-929-{N-[4-(1-Boc-piperidyl)]aminomethyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.23 (d,J = 7.8 Hz, 1H); 7.90 (d, J = 7.5 Hz, 1H); 7.71 (m, 2H); 7.57 (s, 1H);7.43 (m, 1H); 7.34 (d, J = 7.5 Hz, 1H); 3.86 (s, 2H); 3.79 (m, 4H); 2.78(m, 2H); 2.56 (m, 1H); 1.79 (d, J = 12.0 Hz, 2H); 1.37 (s, 9H); 1.15 (m,2H). MS: m/z = 446 (M⁺ − H). IIIb-99-[1-(4-Cyclopentylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO) δ 12.22 (s,1H); 8.22 (d, J = 8.1 Hz, 1H); 7.91 (d, J = 8.1 Hz, 1H); 7.71 (m, 2H);7.51 (s, 1H); 7.44 (m, 1H); 7.28 (d, J = 7.5 Hz, 1H); 3.87 (s, 2H); 3.50(s, 2H); 2.83 (m, 1H); 2.38 (m, 8H); 1.71 (m, 2H); 1.51 (m, 4H); 1.27(m, 2H). MS: m/z = 400 (M⁺ − H). IIIb-109-{1-[4-(2-Ethoxyethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23(d, J = 7.8 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.51 (s,1H); 7.43 (m, 1H); 7.29 (d, J = 7.8 Hz, 1H); 3.87 (s, 2H); 3.50 (s, 2H);3.38 (m, 4H); 2.38 (m, 10H); 1.06 (t, J = 6.9 Hz, 3H). MS: m/z = 404 (M⁺− H). IIb-196 9-{1-[4-(2,2-Diethoxyethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.29 (s, 1H);8.22 (d, J = 7.8 Hz, 1H); 7.91 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.50(s, 1H); 7.43 (m, 1H); 7.28 (d, J = 7.8 Hz, 1H); 4.54 (t, J = 4.8 Hz,1H); 3.87 (s, 2H); 3.50 (m, 6H); 3.38 (m, 8H); 1.07 (t, J = 7.2 Hz, 3H).MS: m/z = 448 (M⁺ − H). IIb-539-[(1-N-Methyl-3-morpholinopropyonyl)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (bs,1H); 8.25 (d, J = 7.5 Hz, 1H); 7.98 (m, 1H); 7.76 (m, 2H); 7.51 (s, 1H);7.47 (m, 1H); 7.26 (m, 1H); 4.67 (s, 1H); 4.59 (s, 1H); 3.83 (m, 2H);3.58-3.49 (m, 4H); 2.96 (s, 2H); 2.84 (s, 1H); 2.73-2.32 (m, 8H).IIIb-16 9-[(4-tert-Butoxycarbonyl-piperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.29 (s, 1H); 8.25(d, J = 7.5 Hz, 1H); 7.95 (d, J = 7.8 Hz, 1H); 7.74 (m, 2H); 7.48 (m,2H); 7.32 (d, J = 7.8, 1H); 3.89 (s, 2H); 3.56 (s, 2H); 3.32 (m, 2H);2.50 (m, 2H); 2.33 (m, 4H); 1.39 (s, 9H). IIb-1059-[(4-Propionyl-piperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.32 (s, 1H); 8.25 (d, J =7.5 Hz, 1H); 7.95 (d, J = 7.8 Hz, 1H); 7.75 (m, 2H); 7.55 (s, 1H); 7.47(m, 1H); 7.33 (d, J = 8.1); 3.90 (s, 2H); 3.57 (s, 2H); 3.44 (m, 4H);2.33 (m, 6H); 0.97 (t, J = 7.5, 3H). MS: m/z = 388 (M⁺ − H). IIIb-189-[4-(2-Hydroxy-2-methyl-propyl-piperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR(DMSO) δ 12.37 (s, 1H); 8.27 (d, J = 7.8 Hz, 1H); 8.05 (m, 1H); 7.78 (m,3H); 7.50 (m, 2H); 3.96 (s, 2H); 3.72-2.73 (m, 12H); 1.20 (s, 6H). MS:m/z = 404 (M⁺ − H). IIb-1189-[(4-Propionyl-homopiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline hydrochloride: ¹H NMR (DMSO) δ 12.39 (s,1H); 10.71 (bs, 1H); 8.27 (d, J = 8.1, 1H); 8.06 (d, J = 7.5 Hz, 1H);7.81 (m, 3H); 7.64 (m, 1H); 7.51 (m, 1H); 4.42 (s, 2H); 4.15-2.99 (m,14H); 0.99 (t, J = 7.2 Hz, 1H). MS: m/z = 402 (M⁺ − H). Dihydrochloride9-[(1-N-Methyl-2-morpholino-aminoethyl)methyl]-5,6- salt of IIIb-19dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR(DMSO) δ 12.41 (s, 1H); 11.64 (bs, 1H); 11.35 (bs, 1H); 8.27 (d, J =6.9, 1H); 8.07 (d, J = 6.9, 1H); 7.90 (s, 1H); 7.74 (m, 3H); 7.51 (m,1H); 4.62 (m, 1H); 4.39 (m, 1H); 3.96 (s, 2H); 3.83-3.17 (m, 12H); 2.73(s, 3H). MS: m/z = 390 (M⁺ − H). IIIa-1110-[S-(3-Fluoropyrrolidino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.30 (s, 1H); 8.24 (d, J =8.1 Hz, 1H); 7.91 (d, J = 7.5); 7.75 (m, 2H); 7.48-7.30 (m, 3H); 5.30(m, 0.5H); 5.11 (m, 0.5H); 3.89 (s, 2H); 3.78 (s, 2H); 2.87-1.86 (m,6H). MS: m/z = 335 (M⁺ − H). IIIa-1210-[(3,4-Dehydropiperidino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.29 (s, 1H); 8.26 (d, J =7.2 Hz, 1H); 7.93 (d, J = 6.6); 7.77 (m, 2H); 7.46-7.33 (m, 3H); 5.67(m, 2H); 3.91 (s, 2H); 3.71 (s, 2H); 2.92 (m, 2H); 2.56 (m, 2H); 2.09(m, 2H). MS: m/z = 329 (M⁺ − H). IIIa-410-[N-1-(3-Hydroxypropyl)aminomethyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.25 (s, 1H); 8.23 (d,J = 8.1 Hz, 1H); 7.87 (dd, J = 2.9 Hz, 5.9 Hz, 1H); 7.75 (m, 2H); 7.44(m, 1H); 7.34 (m, 1H); 3.89 (s, 2H); 3.85 (s, 2H); 3.46 (t, J = 6.3 Hz,2H); 2.60 (t, J = 6.9 Hz, 2H); 1.60 (m, J = 6.3 Hz, 2H). MS: m/z = 321(M⁺ − H). IIIa-110-[1-(4-iso-Propylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23 (d, J =8.1 Hz, 1H); 7.90 (d, J = 7.5 Hz, 1H); 7.75 (m, 2H); 7.44 (m, 1H); 7.35(t, J = 7.2 Hz, 1H); 7.27 (d, J = 7.2 Hz, 1H); 3.89 (s, 2H); 3.59 (s,2H); 2.58 (m, 1H); 2.46-2.35 (m, 8H); 0.92 (d, J = 6.3 Hz, 6H). MS: m/z= 374 (M⁺ − H). IIa-4010-{1-[4-(1-pyrrolidinocarbonylmethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.25(s, 1H); 8.24 (d, J = 8.1 Hz, 1H); 7.90 (d, J = 7.2 Hz, 1H); 7.76 (m,2H); 7.45 (m, 1H); 7.36 (t, J = 7.8 Hz, 1H); 7.28 (d, J = 7.8 Hz, 1H);3.90 (s, 2H); 3.62 (s, 2H); 3.44 (t, J = 6.6 Hz, 2H); 3.24 (t, J = 6.9Hz, 2H); 3.04 (s, 2H); 2.43 (m, 8H); 1.81 (m, 2H); 1.72 (m, 2H). MS: m/z= 443 (M⁺ − H). Dihydrochloride9-[1-(4-Methylhomopiperazino)methyl]-5,6-dihydro-5-oxo- salt of IIIb-1311-H-indeno[1,2-c]isoquinoline dihydrochloride: ¹H NMR (DMSO) δ 12.35(s, 1H); 8.23 (d, J = 7.8 Hz, 1H); 8.02 (d, J = 7.8 Hz, 1H); 7.84 (s,1H); 7.76 (d, J = 3.3 Hz, 2H); 7.65 (d, J = 7.2 Hz, 1H); 7.47 (m, 1H);4.42 (s, 2H); 3.92 (s, 2H); 3.32 (m, 8H); 2.76 (s, 3H); 2.19 (m, 2H).MS: m/z = 360 (M⁺ − H). IIb-669-{1-[4-(2-Cyanoethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.25 (s, 1H); 8.22(d, J = 8.1 Hz, 1H); 7.92 (d, J = 7.5 Hz, 1H); 7.71 (m, 2H); 7.51 (s,1H); 7.44 (m, 1H); 7.29 (d, J = 7.5 Hz, 1H); 3.87 (s, 2H); 3.52 (s, 2H);2.62 (d, J = 6.1 Hz, 2H); 2.54 (d, J = 6.1 Hz, 2H); 2.41 (m, 8H). MS:m/z = 385 (M⁺ − H). Methylsulfonate9-[1-(4,4-Difluoropiperidino)methyl]-5,6-dihydro-5-oxo-11- salt ofIIIb-15 H-indeno[1,2-c]isoquinoline methylsulfonate: ¹H NMR (DMSO) δ12.36 (s, 1H); 9.75 (s, 1H); 8.25 (d, J = 8.1 Hz, 1H); 8.06 (d, J = 8.1Hz, 1H); 7.77 (m, 3H); 7.51 (m, 2H); 4.47 (s, 2H); 3.96 (s, 2H); 3.42(m, 2H); 3.19 (m, 2H); 2.32 (s, 3H); 2.29 (m, 4H). MS: m/z = 367 (M⁺ −H). IIb-79 9-{N-[4-(1-Boc-piperidyl)]-N-cyclopropylaminomethyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s,1H); 8.22 (d, J = 8.1 Hz, 1H); 7.88 (d, J = 8.1 Hz, 1H); 7.71 (m, 2H);7.48 (s, 1H); 7.43 (m, 1H); 7.27 (d, J = 7.8 Hz, 1H); 3.94 (m, 2H); 3.85(s, 2H); 3.81 (s, 2H); 2.61 (m, 3H); 2.01 (m, 1H); 1.74 (m, 2H); 1.36(m, 11H); 0.42 (m, 2H); 0.25 (m, 2H). MS: m/z = 486 (M⁺ − H). IIb-1319-{1-[4-(2-Furyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23 (d, J =8.1 Hz, 1H); 7.92 (d, J = 7.8 Hz, 1H); 7.72 (m, 2H); 7.51 (s, 1H); 7.44(m, 1H); 7.29 (d, J = 8.1 Hz, 1H); 3.88 (m, 3H); 3.68 (dt, J = 6.9 Hz,7.5 Hz, 1H); 3.55 (dt, J = 6.9 Hz, 7.5 Hz, 1H); 3.51 (s, 2H); 2.37 (m,10H); 1.86 (m, 1H); 1.73 (m, 2H); 1.45 (m, 1H). MS: m/z = 416 (M⁺ − H).IIb-157 9-{1-[4-(1-Pyrrolidinocarbonylmethyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c] isoquinoline: ¹H NMR (DMSO) δ 12.27(s, 1H); 8.23 (d, J = 7.8 Hz, 1H); 7.92 (d, J = 8.1 Hz, 1H); 7.72 (m,2H); 7.51 (s, 1H); 7.44 (m, 1H); 7.29 (d, J = 7.8 Hz, 1H); 3.88 (s, 2H);3.51 (m, 2H); 3.43 (t, J = 6.5 Hz, 2H); 3.24 (t, J = 6.6 Hz, 2H); 3.04(s, 2H); 2.38 (m, 8H); 1.77 (m, 4H). MS: m/z = 443 (M⁺ − H). IIIb-209-(N-4-Piperidylaminomethyl)-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.35 (s, 1H); 9.67 (s, 2H);9.04 (s, 1H); 8.90 (s, 1H); 8.25 (d, J = 7.8 Hz, 1H); 8.01 (d, J = 7.8Hz, 1H); 7.83 (s, 1H); 7.77 (m, 2H); 7.63 (d, J = 7.5 Hz, 1H); 7.48 (m,1H); 4.23 (s, 2H); 3.94 (s, 2H); 3.32 (m, 3H); 2.90 (m, 2H); 2.27 (m,2H); 1.92 (m, 2H). MS: m/z = 346 (M⁺ − H). IIIb-89-{1-[4-(2-Pyrimidyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.29 (s, 1H); 8.32 (d,J = 5.1 Hz, 2H); 8.23 (d, J = 8.1 Hz, 1H); 7.94 (d, J = 7.5 Hz, 1H);7.72 (m, 2H); 7.57 (s, 1H); 7.45 (m, 1H); 7.34 (d, J = 7.5 Hz, 1H); 6.59(t, J = 4.8 Hz, 1H); 3.89 (s, 2H); 3.72 (m, 4H); 3.58 (s, 2H); 2.44 (m,4H). MS: m/z = 410 (M⁺ − H). IIb-1709-{1-[4-(Cyclopropylcarbonyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s,1H); 8.24 (d, J = 8.1 Hz, 1H); 7.94 (d, J = 7.8 Hz, 1H); 7.72 (m, 2H);7.55 (s, 1H); 7.45 (m, 1H); 7.33 (d, J = 7.2 Hz, 1H); 3.89 (s, 2H); 3.66(m, 2H); 3.57 (s, 2H); 3.46 (m, 2H); 2.40 (m, 4H); 1.93 (m, 1H); 0.68(m, 4H). MS: m/z = 400 (M⁺ − H). IIIb-219-{1-[4-(Trifluoromethyl)piperidino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.23 (s, 1H); 8.23(d, J = 7.8 Hz, 1H); 7.93 (d, J = 8.1 Hz, 1H); 7.72 (m, 2H); 7.52 (s,1H); 7.44 (m, 1H); 7.30 (d, J = 7.8 Hz, 1H); 3.87 (s, 2H); 3.54 (s, 2H);2.89 (d, J = 11.3 Hz, 2H); 2.21 (m, 1H); 1.97 (t, J = 11.5 Hz, 2H); 1.76(d, J = 11.6 Hz, 2H); 1.45 (m, 2H). MS: m/z = 399 (M⁺ − H). IIIb-229-(1-Homopiperidinomethyl)-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.18 (s, 1H); 8.23 (d, J =7.8 Hz, 1H); 7.90 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.54 (s, 1H); 7.43(m, 1H); 7.31 (d, J = 7.8 Hz, 1H); 3.86 (s, 2H); 3.65 (2, H); 2.57 (m,4H), 1.57 (m, 8H). MS: m/z = 345 (M⁺ − H). IIb-1839-[1-(4-Octylpiperazino)methyl]-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.28 (s, 1H); 8.23 (d, J =8.1 Hz, 1H); 7.93 (d, J = 7.8 Hz, 1H); 7.72 (m, 2H); 7.53 (s, 1H); 7.44(m, 1H); 7.31 (d, J = 7.2 Hz, 1H); 3.88 (s, 2H); 3.58 (s, 2H); 2.87 (m,4H); 2.41 (m, 6H); 1.55 (m, 2H), 1.23 (m, 10H); 0.84 (t, J = 6.9 Hz,3H). MS: m/z = 444 (M⁺ − H). IIIb-239-{1-[4-(3-Hydroxypropyl)piperazino]methyl}-5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline: ¹H NMR (DMSO) δ 12.27 (s, 1H); 8.22(d, J = 7.5 Hz, 1H); 7.92 (d, J = 7.8 Hz, 1H); 7.71 (m, 2H); 7.51 (s,1H); 7.44 (m, 1H); 7.27 (d, J = 7.8 Hz, 1H); 3.87 (s, 2H); 3.51 (s, 2H);3.40 (t, J = 6.3 Hz, 2H); 2.37 (m, 10H); 1.53 (t, J = 6.3 Hz, 3H). MS:m/z = 390 (M⁺ − H). IIb-409-((4-(2-oxo-2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one: ¹H NMR (DMSO-d₆): δ 12.27 (s,1H); 8.23 (d, J = 7.8 Hz, 1H); 7.92 (d, J = 8.1 Hz, 1H); 7.72 (m, 2H);7.51 (s, 1H); 7.43 (t, J = 7.8 Hz, 1H); 7.29 (d, J = 7.8 Hz, 1H); 3.87(s, 2H); 3.51 (s, 2H); 3.43 (t, J = 6.6 Hz, 2H); 3.24 (t, J = 6.6 Hz,2H); 3.04 (s, 2H); 2.38 (m, 8H); 1.80 (m, 2H); 1.72 (m, 2H). IIb-279-((1-(hydroxymethyl)cyclopentylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one: ¹H NMR (DMSO-d₆): δ 12.35 (s, 1H); 8.86(s, 2H); 8.26 (d, J = 8.1 Hz, 1H); 8.03 (d, J = 7.2 Hz, 1H); 7.78 (m,3H); 7.55 (m, 2H); 5.74 (s, 1H); 4.19 (s, 2H); 3.97 (s, 2H); 3.58 (s,2H); 1.76 (m, 6H); 1.58 (m, 2H). MS: m/z 361 (M − H⁺). IIb-2109-((4-(2-(pyrrolidin-1-yl)ethyl)piperidin-1-yl)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one: ¹H NMR (DMSO-d₆): δ 12.24 (s,1H); 8.22 (d, J = 8.1 Hz, 1H); 7.91 (d, J = 7.5 Hz, 1H); 7.70 (m, 2H);7.50 (s, 1H); 7.43 (t, J = 7.8 Hz, 1H); 7.27 (d, J = 7.8 Hz, 1H); 3.86(s, 2H); 3.48 (s, 2H); 2.78 (d, J = 11.1 Hz, 2H); 2.35 (m, 6H); 1.89 (t,J = 10.6 Hz, 2H); 1.62 (m, 6H); 1.35 (m, 3H); 1.15 (m, 2H). MS: m/z 428(M − H⁺). IIa-2810-((1-hydroxymethyl)cyclopentylamino)methyl)benzofuro[3,2-c]isoquinolin-5(6H)-one: ¹H NMR (DMSO-d₆): δ 12.52 (s, 1H); 9.16 (s,2H); 8.35 (d, J = 8.1 Hz, 1H); 8.08 (m, 2H); 7.94 (t, J = 7.5 Hz, 1H);7.69 (t, J = 7.2 Hz, 1H); 7.63 (d, J = 7.8 Hz, 1H); 7.46 (t, J = 7.5 Hz,1H); 5.85 (s, 1H); 4.51 (s, 2H); 3.68 (s, 2H); 1.91 (m, 5H); 1.79 (m,2H); 1.63 (m, 2H). Va-14-chloro-10-((cyclopentylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 8.94 (bs, 2H), 8.13(m, 1H), 7.85 (m, 2H), 7.51 (m, 3H), 4.39 (m, 2H), 4.10 (s, 2H), 3.67(m, 1H), 2.07 (m, 2H), 1.65 (m, 4H), 1.54 (m, 2H). MS: m/z 365.2 (M −H⁺). Va-2 10-((cyclopentylamino)methyl)-2-fluoro-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.46 (bs, 1H), 8.95(bs, 2H), 8.32 (dd, J = 6.0, 6.0 Hz, 1H), 8.07 (dd, J = 2.0, 5.0 Hz,1H), 7.54 (m, 3H), 7.33 (dd, J = 6.0, 6.0 Hz, 1H), 4.29 (m, 2H), 4.06(s, 2H), 3.65 (m, 1H), 2.06 (m, 2H), 1.72 (m, 4H), 1.58 (m, 2H). MS: m/z349.0 (M − H⁺). Va-310-((cyclopentylamino)methyl)-3-fluoro-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.53 (bs, 1H); 8.95(bs, 2H), 8.04 (dd, J = 6.0, 7.2 Hz, 1H), 7.98 (m, 1H), 7.73 (m, 1H),7.51 (m, 2H), 4.31 (dd, J = 5.2, 5.2 Hz, 2H), 4.06 (s, 2H), 3.65 (m,1H), 2.07 (m, 2H), 1.72 (m, 4H), 1.57 (m, 2H). MS: m/z 348.9 (M − H⁺).Va-4 10-((cyclopentylamino)methyl)-4-fluoro-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.37 (bs, 1H), 8.86(bs, 2H); 8.05 (dd, J = 2.0, 6.8 Hz, 1H), 7.77 (m, 1H), 7.54 (m, 3H);7.23 (m, 1H); 4.30 (dd, J = 6.0, 6.0 Hz, 2H); 4.04 (s, 2H); 3.65 (m,1H); 2.31 (m, 2H); 1.71 (m, 4H); 1.57 (m, 2H). MS: m/z 348.9 (M − H⁺)Va-5 3-fluoro-10-((tetrahydro-2H-pyran-4-ylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.47(bs, 1H), 8.85 (bs, 2H), 7.98 (d, J = 6.5 Hz, 2H), 7.67 (m, 1H), 7.44(m, 3H), 4.38 (m, 2H), 4.27 (m, 2H), 3.99 (dd, J = 3.6, 11.6 Hz, 2H),3.53 (m, 2H), 3.42 (m, 1H), 2.01 (m, 2H), 1.58 (m, 2H) MS: m/z 365.30 (M− H+). Va-6 1-fluoro-10-((tetrahydro-2H-pyran-4-ylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.49(bs, 1H), 8.93 (bs, 2H). 8.65 (m, 1H), 7.95 (dd, J = 2.0, 8.9 Hz, 1H),7.89 (dd, J = 2.5, 8.9, 1H), 7.75 (m, 2H), 7.42 (dd, J = 4.0, 8.0 Hz,1H), 5.81 (bs, 1H), 4.28 (m, 2H), 4.07 (s, 2H), 3.65 (m, 2H), 3.49 (m,1H), 1.84 (m, 8H). MS: m/z 379.2 (M − H⁺) Va-710-((cyclopentylamino)methyl)-1-fluoro-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.58 (bs, 1H), 8.94(bs, 2H), 8.13 (d, J = 2.8, 7,6 Hz, 2H), 7.65 (m, 1H), 7.51 (m, 3H),4.34 (dd, J = 6.0, 6.0 Hz, 2H), 4.20 (s, 2H), 3.67 (m, 1H), 2.07 (m,2H), 1.69 (m, 4H), 1.57 (m, 2H). MS: m/z 348.9 (M − H⁺). Va-82-fluoro-10-((tetrahydro-2H-pyran-4-ylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.70(bs, 1H), 9.16 (bs, 2H), 8.57 (m, 1H), 8.33 (m, 1H), 7.77 (m, 3H), 7.55(m, 1H), 4.60 (m, 2H), 4.27 (m, 2H), 4.21 (m, 2H), 3.65 (m, 2H), 3.55(m, 1H), 2.31 (m, 2H), 1.92 (m, 2H). MS: m/z 365.3 (M − H⁺). Va-98-fluoro-10-((1-(hydroxymethyl)cyclopentylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO-d₆).: δ 12.59(bs, 1H), 8.90 (bs, 2H); 8.12 (d, J = 8.0 Hz, 2H), 7.65 (m, 1H), 7.52(m, 3H), 4.38 (m, 2H), 4.20 (s, 2H), 3.97 (dd J = 2.0, 10 Hz, 2H), 3.55(m, 2H), 3.42 (m, 1H), 2.13 (m, 2H); 1.65 (m, 2H). MS: m/z 365.3 (M −H⁺). Va-10 3,8-difluoro-10-((1-(hydroxymethyl)cyclopentylamino)methyl)-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one ¹H NMR (DMSO- d₆).: δ12.49 (bs, 1H); 9.12 (bs, 2H), 8.66 (m, 1H), 7.96 (m, 2H), 7.89 (m, 1H);7.75 (m, 1H), 5.84 (bs, 1H), 4.28 (m, 2H), 4.07 (s, 2H), 3.65 (m, 2H);3.45 (m, 1H), 1.84 (m, 4H), 1.64 (m, 4H). MS: m/z 397.2 (M − H⁺).

Example 2 Determination of the Effect of Indenoisoquinolinone Analogs onin vitro PARP Activity

The ability of an illustrative Indenoisoquinolinone Analog to inhibitPARP and prevent peroxynitrite induced cytotoxicity can be demonstratedusing methods described in Virag et al., Br. J. Pharmacol. 1999,126(3):769-77; and Immunology 1998, 94(3):345-55.

The potency of inhibition of purified PARP enzyme can be subsequentlydetermined for selected Indenoisoquinolinone Analogs, and the potency iscompared with that of 3-aminobenzamide, a prototypical benchmark PARPinhibitor. The assay is performed in 96 well ELISA plates according toinstructions provided with a commercially available PARP inhibitionassay kit (for example, from Trevigen, Gaithersburg, Md.).

Example 3 Determination of the Effect of Indenoisoquinolinone Analogs inan In Vitro Model of Cell Death

Using an in vitro, oxidant-stimulated thymocyte assay (described, indetail, in Virag et al., Immunology 94(3):345-55, 1998), an illustrativeIndenoisoquinolinone Analog can be tested for its ability to prevent theoxidant-induced suppression of the viability of the cells and as such,this assay represents an in vitro model of reperfusion related celldeath in ischemic organs.

Example 4 Determination of the Effect of Indenoisoquinolinone Analogs onin vivo Models of Inflammatory Diseases

The effect of an illustrative Indenoisoquinolinone Analog can bedetermined using a systemic inflammatory model induced by bacteriallipopolysaccharide (LPS), which is reported to be responsible forcausing reperfusion injurys and inflammatory diseases such as septicshock and systemic inflammatory response syndrome in animals (seeParrillo, N. Engl. J. Med., 328:1471-1478 (1993) and Lamping, J. Clin.Invest. 101:2065-2071 (1998).

Example 5 Determination of the Effect of Indenoisoquinolinone Analogs onIn Vivo Models of Reperfusion injury

The efficacy of an illustrative Indenoisoquinolinone Analog in a mousemodel of ischemic and reperfused gut can be determined according to themethod described in Liaudet et al., Shock 2000, 14(2):134-41.

In another set of experiments, the effect of an illustrativeIndenoisoquinolinone Analog in a rat model of middle cerebral arteryocclusion/reperfusion can be assayed as described in Abdelkarim et al,Int. J. Mol. Med. 2001, 7(3):255-60.

Example 6 Determination of the Effect of Indenoisoquinolinone Analogs inan In Vivo Model of Diabetes Mellitus

PARP inhibitors and PARP deficiency are known to reduce the developmentof diabetes mellitus and the incidence of diabetic complications. Theanti-diabetic effect of an illustrative Indenoisoquinolinone Analog canbe determined using a single high-dose streptozotocin model of diabetesmellitus, which can be used as conducted as described in Mabley et al.,Br. J. Pharmacol. 2001, 133(6):909-9; and Soriano et al., Nat. Med.2001, 7(1): 108-13. Briefly, 160 mg/kg streptozotocin is injected tomice treated with vehicle (control) or with an illustrativeIndenoisoquinolinone Analog intraperitoneally (3 mg/kg) and 3 days laterblood sugar levels are determined using a blood glucose meter.

Example 7 Determination of the Effect of Indenoisoquinolinone Analogs inan In Vivo Model of Erectile Dysfunction

Experiments are conducted in male Sprague-Dawley rats according topreviously published methods for forceps-induced nerve crush injury anderectile function measurements (Rehman, J., et al., Urology 51:640-644,1998; Sezen, S. F., et al., Int. J. Impot. Res. 14:506-12, 2002).Subjects are anesthetized with Phenobarbital. The prostate of thesubjects is exposed and the cavernosal nerve is clipped on either sidewith a forceps to induce mechanical injury (crush). This rat modelmimics the nerve injury that develops during human male prostatectomy,leading to nerve injury and subsequent erectile dysfunction. Subjectsare studied 2 weeks after the injury. Two groups of subjects are used,one group treated with vehicle and one group treated with anillustrative Indenoisoquinolinone Analog. The illustrativeIndenoisoquinolinone Analog is injected at 30 mg/kg i.v. immediatelybefore the crush injury, and on the following day at the same dose.Thereafter, for 12 days, subjects are treated with 60 mg/kg of theillustrative Indenoisoquinolinone Analog intraperitoneally. At 2 weeks,subjects are re-anesthetized and measured for mean arterial bloodpressure (MAP) and intracavernosal pressure (ICP). Cavernosal nervestimulation is conducted at 5 and 7.5 V using a square pulse stimulatorfor 30 msec. ICP is determined as the area under curve (mmHg X sec). Inaddition, IPC/MAP ratios are determined.

Example 8 Effect of Indenoisoquinolinone Analogs on PARP Activity inCultured Macrophages, Using a Whole-Cell Based Assay

Demonstration of Indenoisoquinolinone Analogs' ability to inhibit PARPand prevent peroxynitrite induced cytotoxicity was shown using methodsdescribed in Virag et al., Br. J. Pharmacol. 1999, 126(3):769-77; andImmunology 1998, 94(3):345-55. The murine RAW macrophages (ATCC,American Type Culture Collection, Manassas, Va.) were grown in RPMI 1650(Invitrogen Life Technologies; Carlsbad, Calif.) medium supplementedwith 10% heat-inactivated FBS, 2 mM L-glutamine, and 100 U/ml ofpenicillin and streptomycin. Cells, between passages 5 and 15, wereseeded at a density of 250,000 cells/well in 12 well plates and allowedto grow 48 hours before use. Growth medium was changed on the day ofuse. Cells were treated with an Indenoisoquinolinone Analog diluted in agrowth medium supplemented with 10% fetal bovine serum (FBS) for 1 hourprior to the addition of hydrogen peroxide (0.5 mM) for a further 25minutes. For the measurement of PARP activity, media was removed andreplaced with 0.5 ml of the assay buffer (56 mM HEPES-pH 7.5, 28 mM KCl,28 mM NaCl, 2 mM MgCl₂, 0.01% digitonin, and 0.5 μCi/ml of 3H-NAD⁺) for20 minutes. After aspirating the assay buffer, cells were lysed andtransferred to eppendorf tubes containing 250 μl of 50% ice-coldtrichloroacetic acid (TCA), which were then placed at 4° C. for 4 hours.Samples were centrifuged at 10,000 g for 10 minutes and supernatantremoved. The pellets were washed twice with 500 μl of ice-cold 5% w/vTCA. The pellets were then solubilized in 250 μl of NaOH (0.1 M)containing 2% SDS overnight at 37° C. and the PARP activity was thendetermined by measuring the radioactivity incorporated using a Wallacscintillation counter. The solubilized protein (250 μl) was mixed with 5ml of scintillation fluid (ScintiSafe Plus, Fisher Scientific) beforebeing counted for 3 minutes. EC₅₀ values were determined from adose-response curve.

TABLE 4 Compound EC₅₀ value [nM] IIa-1 20 IIa-14 30 IIa-27 <10 IIIa-2 25IIIa-3 20 IIIa-4 15 IIIa-5 40 IIIa-6 50 IIIa-7 60 IIIa-8 75 IIIa-9 60IIIa-10 60 IIIa-11 12 IIIa-12 7 IIb-1 45 IIb-53 >50 IIb-66 45 IIb-79 >60IIb-92 >60 IIb-105 100 IIb-118 60 IIb-170 75 IIb-131 75 IIb-196 75IIb-183 100 IIb-157 75 IIIb-1 20 IIIb-2 25 Dihydrochloride 10 salt ofIIIb-3 IIIb-8 75 IIIb-9 20 IIIb-10 75 IIIb-13 25 Dihydrochloride 20 saltof IIIb-14 Methylsulfonate 55 salt of IIIb-15 IIIb-16 >100 IIIb-17 100IIIb-18 75 IIIb-19 30 Dihydrochloride 100 salt of IIIb-20 IIIb-21 100IIIb-22 >100 IIIb-24 >60 IIIa-1 45 IIb-23 80 Va-1 >100 Va-3 9 Va-4 4Va-5 5 Va-7 5 Va-9 3 Va-10 3

The present invention is not to be limited in scope by the specificembodiments disclosed in the examples, which are intended asillustrations of a few aspects of the invention and any embodiments thatare functionally equivalent are within the scope of this invention.Indeed, various modifications of the invention in addition to thoseshown and described herein will become apparent to those skilled in theart and are intended to fall within the scope of the appended claims.

A number of references have been cited, the entire disclosures of whichhave been incorporated herein in their entirety.

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —N(C₁-C₄alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-; R¹ is—(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²); each R² is independently—H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, —C₁-C₆ alkylene phenyl,phenyl, an N-terminal alpha amino acid residue, an N-terminal alphaamino hydroxymethyl residue, a C₁-C₆ alkyl ester of an N-terminal alphaamino acid residue, or a nitrogen-containing 3- to 7-membered monocyclicheterocycle, each of which other than hydrogen is independentlyunsubstituted or substituted with one or more of -halo, —OH,—OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocycliccycloalkyl, a 3- to 7-membered monocyclic heterocycle, —(C₁-C₆alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; m is an integer ranging from 2 to 10; p isan integer ranging from 1 to 5; and q is an integer ranging from 1 to 5.2. The compound or a pharmaceutically acceptable salt of the compound ofclaim 1, wherein X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))-, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or-phenyl, each of which other than hydrogen is unsubstituted orsubstituted with one or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, or—(C₁-C₅ alkylene)-O—C₁-C₅ alkyl, each of which other than hydrogen isunsubstituted or substituted with one or more of -halo, —OH or —NH₂; orN, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; or N and bothR² groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; n is an integerranging from 1 to 10; and m is an integer ranging from 2 to
 10. 3. Thecompound or a pharmaceutically acceptable salt of the compound of claim1, wherein X is —N(CH₃)—.
 4. The compound or a pharmaceuticallyacceptable salt of the compound of claim 1, wherein at least one R² is—C₁-C₆ alkyl or —C₃-C₈ monocyclic cycloalkyl.
 5. The compound or apharmaceutically acceptable salt of the compound of claim 1, wherein nis
 1. 6. The compound or a pharmaceutically acceptable salt of thecompound of claim 1, wherein each R² is independently —C₁-C₆ alkyl. 7.The compound or a pharmaceutically acceptable salt of the compound ofclaim 1, wherein one R² is —H.
 8. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —N(C₁-C₄alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-; R¹ is—(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²); each R² is independently—H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, —C₁-C₆ alkylene phenyl,phenyl, an N-terminal alpha amino acid residue, an N-terminal alphaamino hydroxymethyl residue, a C₁-C₆ alkyl ester of an N-terminal alphaamino acid residue, or a nitrogen-containing 3- to 7-membered monocyclicheterocycle, each of which other than hydrogen is independentlyunsubstituted or substituted with one or more of -halo, —OH,—OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocycliccycloalkyl, a 3- to 7-membered monocyclic heterocycle, —(C₁-C₆alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; m is an integer ranging from 2 to 10; p isan integer ranging from 1 to 5; and q is an integer ranging from 1 to 5.9. The compound or a pharmaceutically acceptable salt of the compound ofclaim 1, wherein X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, —(C₁-C₆ alkylene)-phenyl or-phenyl, each of which other than hydrogen is unsubstituted orsubstituted with one or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, or—(C₁-C₅ alkylene)-O—C₁-C₅ alkyl, each of which other than hydrogen isunsubstituted or substituted with one or more of -halo, —OH or —NH₂; orN, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; or N and bothR² groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; n is an integerranging from 1 to 10; and m is an integer ranging from 2 to
 10. 10. Thecompound or a pharmaceutically acceptable salt of the compound of claim8, wherein X is —N(CH₃)—.
 11. The compound or a pharmaceuticallyacceptable salt of the compound of claim 8, wherein at least one R² is—C₁-C₆ alkyl or —C₃-C₈ monocyclic cycloalkyl.
 12. The compound or apharmaceutically acceptable salt of the compound of claim 8, wherein nis
 1. 13. The compound or a pharmaceutically acceptable salt of thecompound of claim 8, wherein each R² is independently —C₁-C₆ alkyl. 14.The compound or a pharmaceutically acceptable salt of the compound ofclaim 8, wherein one R² is —H.
 15. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —N(C₁-C₄alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)- or —N((CH₂)_(q)-Z)-; R¹ is—(CH₂)_(n)—N(R²)(R²) or —O—(CH₂)_(m)—N(R²)(R²); each R² is independently—H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl, —C₁-C₆ alkylene phenyl,phenyl, an N-terminal alpha amino acid residue, an N-terminal alphaamino hydroxymethyl residue, a C₁-C₆ alkyl ester of an N-terminal alphaamino acid residue, or a nitrogen-containing 3- to 7-membered monocyclicheterocycle, each of which other than hydrogen is independentlyunsubstituted or substituted with one or more of -halo, —OH,—OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈ monocycliccycloalkyl, a 3- to 7-membered monocyclic heterocycle, —(C₁-C₆alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R³)₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; m is an integer ranging from 2 to 10; p isan integer ranging from 1 to 5; and q is an integer ranging from 1 to 5.16. The compound or a pharmaceutically acceptable salt of the compoundof claim 15, wherein X is —N(CH₃)—, —N(CH₂CH₃)—, —N(CH₂CH₂CH₃)—, —N(CH₂CH₂CH₂CH₃)—, —N(C(H)(CH₃)(CH₂CH₃))—, —N(C(H)(CH₃)₂)—, —N(CH₂C(H)(CH₃)₂)—or —N(C(CH₃)₃)—; each R² is independently —H, —C₁-C₆ alkyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, (C₁-C₆ alkylene)-phenyl or -phenyl,each of which other than hydrogen is unsubstituted or substituted withone or more of -halo, —OH, —OP(O)(OH)₂, —OS(O)₂OH or —N(Z₃)(Z₄), whereZ₃ and Z₄ are independently —H, —C₁-C₅ alkyl, or —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, each of which other than hydrogen isunsubstituted or substituted with one or more of -halo, —OH or —NH₂; orN, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; or N and bothR² groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one to three of —C₁-C₅ alkyl, -phenyl, —(C₁-C₅ alkylene)-phenyl,-(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted) C₁-C₅alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, or —C₁-C₁₀ alkyl; n is an integerranging from 1 to 10; and m is an integer ranging from 2 to
 10. 17. Thecompound or a pharmaceutically acceptable salt of the compound of claim15, wherein X is —N(CH₃)—.
 18. The compound or a pharmaceuticallyacceptable salt of the compound of claim 15, wherein at least one R² is—C₁-C₆ alkyl or —C₃-C₈ monocyclic cycloalkyl.
 19. The compound or apharmaceutically acceptable salt of the compound of claim 15, wherein nis
 1. 20. The compound or a pharmaceutically acceptable salt of thecompound of claim 15, wherein each R² is independently —C₁-C₆ alkyl. 21.The compound or a pharmaceutically acceptable salt of the compound ofclaim 15, wherein one R² is —H.
 22. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —CH₂—, —O—,—C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—; R¹ is—(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl; R³ is—C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle), anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups; or N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which is substituted with one or more of —C₂-C₆ alkenyl,—C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl),—C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂,-(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle) or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle) groups; and an n is an integer ranging from 1 to
 10. 23.The compound or a pharmaceutically acceptable salt of the compound ofclaim 22, wherein, X is —CH₂—.
 24. The compound or a pharmaceuticallyacceptable salt of the compound of claim 22, wherein R² is —H, and R³ isa nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl groups.
 25. Thecompound or a pharmaceutically acceptable salt of the compound of claim22, wherein X is —CH₂— and R³ is —C₃-C₈ monocyclic cycloalkyl which issubstituted with one or more of hydroxy-substituted C₁-C₅ alkyl groups.26. The compound or a pharmaceutically acceptable salt of the compoundof claim 22, wherein X is —CH₂— and R³ is —C(O)—C₁-C₆ alkylene-3- to7-membered monocyclic heterocycle.
 27. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —CH₂—, —O—,—C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—; R¹ is—(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl; R³ is—C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle), anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups; or N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which is substituted with one or more of —C₂-C₆ alkenyl,—C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl),—C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂,-(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle) or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle) groups; and an n is an integer ranging from 1 to
 10. 28.The compound or a pharmaceutically acceptable salt of the compound ofclaim 27, wherein, X is —CH₂—.
 29. The compound or a pharmaceuticallyacceptable salt of the compound of claim 27, wherein R² is —H, and R³ isa nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl groups.
 30. Thecompound or a pharmaceutically acceptable salt of the compound of claim27, wherein X is —CH₂— and R³ is —C₃-C₈ monocyclic cycloalkyl which issubstituted with one or more of hydroxy-substituted C₁-C₅ alkyl groups.31. The compound or a pharmaceutically acceptable salt of the compoundof claim 27, wherein X is —CH₂— and R³ is —C(O)—C₁-C₆ alkylene-3- to7-membered monocyclic heterocycle.
 32. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —CH₂—, —O—,—C(O)—, —CH(OH)—, —NH—, —N(C₁-C₄ alkyl)- or —S—; R¹ is—(CH₂)_(n)—N(R²)(R³) or

R² is —H, —C₁-C₆ alkyl, or —C₃-C₈ monocyclic cycloalkyl; R³ is—C(O)—(C₁-C₆ alkylene)-(3- to 7-membered monocyclic heterocycle), anitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl, or —C₃-C₈ monocycliccycloalkyl which is substituted with one or more of(hydroxy-substituted) C₁-C₅ alkyl groups; or N, R² and R³ are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle, which is substituted with one or more of —C₂-C₆ alkenyl,—C(O)—C₁-C₆ alkyl, —(C₁-C₄ alkylene)-C(O)—(C₃-C₈ monocyclic cycloalkyl),—C₇-C₁₀ alkyl, —(C₁-C₅ alkylene)-C(H)(—O—C₁-C₄ alkyl)₂,-(cyano-substituted) C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)-(nitrogen-containing 3- to 7-membered monocyclicheterocycle) or —(C₁-C₅ alkylene)-(3- to 7-membered monocyclicheterocycle) groups; and an n is an integer ranging from 1 to
 10. 33.The compound or a pharmaceutically acceptable salt of the compound ofclaim 32, wherein, X is —CH₂—.
 34. The compound or a pharmaceuticallyacceptable salt of the compound of claim 32, wherein R² is —H, and R³ isa nitrogen-containing 3- to 7-membered monocyclic heterocycle which issubstituted with one or more of —C(O)O—C₁-C₆ alkyl groups.
 35. Thecompound or a pharmaceutically acceptable salt of the compound of claim32, wherein X is —CH₂— and R³ is —C₃-C₈ monocyclic cycloalkyl which issubstituted with one or more of hydroxy-substituted C₁-C₅ alkyl groups.36. The compound or a pharmaceutically acceptable salt of the compoundof claim 32, wherein X is —CH₂— and R³ is —C(O)—C₁-C₆ alkylene-3- to7-membered monocyclic heterocycle.
 37. A composition comprising aphysiologically acceptable carrier or vehicle and an effective amount ofa compound or a pharmaceutically acceptable salt of a compound ofclaim
 1. 38. A composition comprising a physiologically acceptablecarrier or vehicle and an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim
 8. 39. Acomposition comprising a physiologically acceptable carrier or vehicleand an effective amount of a compound or a pharmaceutically acceptablesalt of a compound of claim
 15. 40. A composition comprising aphysiologically acceptable carrier or vehicle and an effective amount ofa compound or a pharmaceutically acceptable salt of a compound of claim22.
 41. A composition comprising a physiologically acceptable carrier orvehicle and an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim
 27. 42. A composition comprisinga physiologically acceptable carrier or vehicle and an effective amountof a compound or a pharmaceutically acceptable salt of a compound ofclaim
 32. 43. A method for treating cancer, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 1 to a subject in need thereof.
 44. A method fortreating cancer, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 8to a subject in need thereof.
 45. A method for treating cancer,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 46. A method for treating cancer, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 22 to a subject in need thereof.47. A method for treating cancer, comprising administering an effectiveamount of a compound or a pharmaceutically acceptable salt of a compoundof claim 27 to a subject in need thereof.
 48. A method for treatingcancer, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 49. The method of claim 43, further comprisingadministering an effective amount of another anticancer agent.
 50. Themethod of claim 44, further comprising administering an effective amountof another anticancer agent.
 51. The method of claim 45, furthercomprising administering an effective amount of another anticanceragent.
 52. The method of claim 46, further comprising administering aneffective amount of another anticancer agent.
 53. The method of claim47, further comprising administering an effective amount of anotheranticancer agent.
 54. The method of claim 48, further comprisingadministering an effective amount of another anticancer agent.
 55. Amethod for treating renal failure, comprising administering an effectiveamount of a compound or a pharmaceutically acceptable salt of a compoundof claim 1 to a subject in need thereof.
 56. A method for treating renalfailure, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 57. A method for treating renal failure, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 15 to a subject in need thereof.58. A method for treating renal failure, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 22 to a subject in need thereof.
 59. A method fortreating renal failure, comprising administering an effective amount ofa compound or a pharmaceutically acceptable salt of a compound of claim27 to a subject in need thereof.
 60. A method for treating renalfailure, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 61. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 62. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 63. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 64. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 65. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 66. A method for treating a reperfusion injury,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 67. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 68. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 69. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 70. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 71. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 72. A method for treating an inflammatory disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 73. A method for treating diabetes mellitus, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 1 to a subject in need thereof.74. A method for treating diabetes mellitus, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 8 to a subject in need thereof.
 75. A method fortreating diabetes mellitus, comprising administering an effective amountof a compound or a pharmaceutically acceptable salt of a compound ofclaim 15 to a subject in need thereof.
 76. A method for treatingdiabetes mellitus, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 22to a subject in need thereof.
 77. A method for treating diabetesmellitus, comprising administering an effective amount of a compound ora pharmaceutically acceptable salt of a compound of claim 27 to asubject in need thereof.
 78. A method for treating diabetes mellitus,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 79. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 80. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 81. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 82. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 83. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 84. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 85. A method for treating reoxygenation injuryresulting from organ transplantation, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 1 to a subject in need thereof.
 86. A method fortreating reoxygenation injury resulting from organ transplantation,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 87. A method for treating reoxygenation injuryresulting from organ transplantation, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 15 to a subject in need thereof.
 88. A method fortreating reoxygenation injury resulting from organ transplantation,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 89. A method for treating reoxygenation injuryresulting from organ transplantation, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 27 to a subject in need thereof.
 90. A method fortreating reoxygenation injury resulting from organ transplantation,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 91. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 92. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 93. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 94. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 95. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 96. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 97. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 98. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 99. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 100. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 101. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 102. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 103. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 104. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 105. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 106. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 107. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 108. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 109. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 110. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 111. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 112. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 113. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 114. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 115. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 116. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 117. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 118. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 119. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 120. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 121. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 122. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 123. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 15 to a subjectin need thereof.
 124. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 125. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 27 to a subjectin need thereof.
 126. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 127. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 1 to asubject in need thereof.
 128. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 8 to asubject in need thereof.
 129. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 15 to asubject in need thereof.
 130. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 22 to asubject in need thereof.
 131. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 27 to asubject in need thereof.
 132. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 32 to asubject in need thereof.
 133. A method for treating cardiomyopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 1 to a subjectin need thereof.
 134. A method for treating cardiomyopathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 8 to a subject in need thereof.135. A method for treating cardiomyopathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 15 to a subject in need thereof.
 136. A method fortreating cardiomyopathy, comprising administering an effective amount ofa compound or a pharmaceutically acceptable salt of a compound of claim22 to a subject in need thereof.
 137. A method for treatingcardiomyopathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 27to a subject in need thereof.
 138. A method for treating cardiomyopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 139. A method for treating retinopathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 1 to a subject in need thereof.140. A method for treating retinopathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 8 to a subject in need thereof.
 141. A method fortreating retinopathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 15to a subject in need thereof.
 142. A method for treating retinopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 143. A method for treating retinopathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 27 to a subject in need thereof.144. A method for treating retinopathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 32 to a subject in need thereof.
 145. A method fortreating nephropathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 1to a subject in need thereof.
 146. A method for treating nephropathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 8 to a subjectin need thereof.
 147. A method for treating nephropathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 15 to a subject in need thereof.148. A method for treating nephropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 22 to a subject in need thereof.
 149. A method fortreating nephropathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 27to a subject in need thereof.
 150. A method for treating nephropathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 32 to a subjectin need thereof.
 151. A method for treating neuropathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 1 to a subject in need thereof.152. A method for treating neuropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 8 to a subject in need thereof.
 153. A method fortreating neuropathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim 15to a subject in need thereof.
 154. A method for treating neuropathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 22 to a subjectin need thereof.
 155. A method for treating neuropathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 27 to a subject in need thereof.156. A method for treating neuropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 32 to a subject in need thereof.
 157. A compoundhaving the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —O—, —CH₂—,—C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)-or —N((CH₂)_(q)-Z)-; R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²); eachR² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂,—C₁-C₅-alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; p is an integer ranging from 1 to 5; and qis an integer ranging from 1 to
 5. 158. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —O—, —CH₂—,—C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)-or —N((CH₂)_(q)-Z)-; R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²); eachR² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; p is an integer ranging from 1 to 5; and qis an integer ranging from 1 to
 5. 159. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein X is —O—, —CH₂—,—C(O)—, —NH—, —S—, —N(C₁-C₄ alkyl)-, —CH(OH)—, —N(C(O)N(H)—(CH₂)_(p)-Z)-or —N((CH₂)_(q)-Z)-; R¹ is —O—C(C₁-C₃ alkyl)₂—(CH₂)_(n)—N(R²)(R²); eachR² is independently —H, —C₁-C₆ alkyl, —C₃-C₈ monocyclic cycloalkyl,—C₁-C₆ alkylene phenyl, phenyl, an N-terminal alpha amino acid residue,an N-terminal alpha amino hydroxymethyl residue, a C₁-C₆ alkyl ester ofan N-terminal alpha amino acid residue, or a nitrogen-containing 3- to7-membered monocyclic heterocycle, each of which other than hydrogen isindependently unsubstituted or substituted with one or more of -halo,—OH, —OP(O)(OH)₂, —OS(O)₂OH, —C₁-C₆ alkyl, —O—C₁-C₆ alkyl, —C₃-C₈monocyclic cycloalkyl, a 3- to 7-membered monocyclic heterocycle,—(C₁-C₆ alkyl-substituted) 3- to 7-membered monocyclic heterocycle, or—N(Z₃)(Z₄), where Z₃ and Z₄ are independently —H, —C₁-C₅ alkyl, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, benzyl, or —C₃-C₈ monocyclic cycloalkyl, eachof which other than hydrogen is independently unsubstituted orsubstituted with one or more of -halo, —OH, —N(R^(a))₂, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —NH₂, a nitrogen-containing 3- to 7-memberedmonocyclic heterocycle, or a —(C₁-C₆ alkyl-substituted)nitrogen-containing 3- to 7-membered monocyclic heterocycle, whereineach occurrence of R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl;or N, Z₃ and Z₄ are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle which is unsubstituted or substitutedwith one or more of —C₁-C₅ alkyl, phenyl, -(phenyl-substituted) C₁-C₅alkyl, -(hydroxy-substituted) C₁-C₅ alkyl, -halo, -(halo-substituted)C₁-C₅ alkyl, -(halo-substituted) phenyl, -phenylene-O—C₁-C₅ alkyl,-(cyano-substituted) phenyl, —OH, —O—C₁-C₅ alkyl, —N(R^(a))₂, —(C₁-C₅alkylene)-N(R^(a))₂, —(C₁-C₅ alkylene)-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂,—COOH, —(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, benzyl, or —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; or N and both R² groups are takentogether to form a nitrogen-containing 3- to 7-membered monocyclicheterocycle or a nitrogen-containing 7- to 10-membered bicyclicheterocycle, each of which is unsubstituted or substituted with one ormore of —C₁-C₅ alkyl, —C₃-C₈ monocyclic cycloalkyl, phenyl, anitrogen-containing 3- to 7-membered monocyclic heterocycle,-(phenyl-substituted) C₁-C₅ alkyl, -(hydroxy-substituted) C₁-C₅ alkyl,-halo, -(halo-substituted) C₁-C₅ alkyl, -(halo-substituted) phenyl,-phenylene-O—C₁-C₅ alkyl, -(cyano-substituted) phenyl, —OH, —O—C₁-C₅alkyl, —N(R^(a))₂, —(C₁-C₅ alkylene)-N(R^(a))₂, —C₁-C₅alkylene-C(O)O—(C₁-C₅ alkylene)-N(R^(a))₂, —COOH, —(C₁-C₅alkylene)-O—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C₃-C₈ monocyclic cycloalkyl,—(C₁-C₅ alkylene)-COOH, —OP(O)(OH)₂, —OS(O)₂OH, —(C₁-C₅alkylene)-OP(O)(OH)₂, —(C₁-C₅ alkylene)-OS(O)₂OH, —C(O)O—C₁-C₅ alkyl,—OC(O)—C₁-C₅ alkyl, —(C₁-C₅ alkylene)-C(O)O—C₁-C₅ alkyl, —(C₁-C₅alkylene)-C(O)NH—C₁-C₅ alkyl, —C(O)NH₂, or —NO₂, wherein each occurrenceof R^(a) is independently —H, -benzyl, —C₁-C₁₀ alkyl; or N and bothR^(a) groups are taken together to form a nitrogen-containing 3- to7-membered monocyclic heterocycle; Z is —CF₃, —F, —OH or —O—CH₃; n is aninteger ranging from 1 to 10; p is an integer ranging from 1 to 5; and qis an integer ranging from 1 to
 5. 160. A composition comprising aphysiologically acceptable carrier or vehicle and an effective amount ofa compound or a pharmaceutically acceptable salt of a compound of claim159.
 161. A composition comprising a physiologically acceptable carrieror vehicle and an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim
 157. 162. A compositioncomprising a physiologically acceptable carrier or vehicle and aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim
 158. 163. A method for treating cancer, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 159 to a subject in need thereof.164. A method for treating cancer, comprising administering an effectiveamount of a compound or a pharmaceutically acceptable salt of a compoundof claim 157 to a subject in need thereof.
 165. A method for treatingcancer, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 166. The method of claim 165, further comprisingadministering an effective amount of another anticancer agent.
 167. Themethod of claim 163, further comprising administering an effectiveamount of another anticancer agent.
 168. The method of claim 164,further comprising administering an effective amount of anotheranticancer agent.
 169. A method for treating renal failure, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 159 to a subject in need thereof.170. A method for treating renal failure, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 157 to a subject in need thereof.
 171. A method fortreating renal failure, comprising administering an effective amount ofa compound or a pharmaceutically acceptable salt of a compound of claim158 to a subject in need thereof.
 172. A method for treating areperfusion injury, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim159 to a subject in need thereof.
 173. A method for treating areperfusion injury, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim157 to a subject in need thereof.
 174. A method for treating areperfusion injury, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim158 to a subject in need thereof.
 175. A method for treating aninflammatory disease, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim159 to a subject in need thereof.
 176. A method for treating aninflammatory disease, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim157 to a subject in need thereof.
 177. A method for treating aninflammatory disease, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim158 to a subject in need thereof.
 178. A method for treating diabetesmellitus, comprising administering an effective amount of a compound ora pharmaceutically acceptable salt of a compound of claim 159 to asubject in need thereof.
 179. A method for treating diabetes mellitus,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 180. A method for treating diabetes mellitus,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 181. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 182. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 183. A method for treating an ischemic condition,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 184. A method for treating reoxygenation injuryresulting from organ transplantation, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 159 to a subject in need thereof.
 185. A method fortreating reoxygenation injury resulting from organ transplantation,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 186. A method for treating reoxygenation injuryresulting from organ transplantation, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 158 to a subject in need thereof.
 187. A method fortreating a neurodegenerative disease, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 159 to a subject in need thereof.
 188. A method fortreating a neurodegenerative disease, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 157 to a subject in need thereof.
 189. A method fortreating a neurodegenerative disease, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 158 to a subject in need thereof.
 190. A method fortreating a vascular disease, comprising administering an effectiveamount of a compound or a pharmaceutically acceptable salt of a compoundof claim 159 to a subject in need thereof.
 191. A method for treating avascular disease, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim157 to a subject in need thereof.
 192. A method for treating a vasculardisease, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 193. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 194. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 195. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 196. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 197. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 198. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 199. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 200. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 201. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 202. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 203. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 157 to a subjectin need thereof.
 204. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 205. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 159 to asubject in need thereof.
 206. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 157 to asubject in need thereof.
 207. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 158 to asubject in need thereof.
 208. A method for treating cardiomyopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 209. A method for treating cardiomyopathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 157 to a subject in need thereof.210. A method for treating cardiomyopathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 158 to a subject in need thereof.
 211. A method fortreating retinopathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim159 to a subject in need thereof.
 212. A method for treatingretinopathy, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 157 to asubject in need thereof.
 213. A method for treating retinopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 158 to a subjectin need thereof.
 214. A method for treating nephropathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 159 to a subject in need thereof.215. A method for treating nephropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 157 to a subject in need thereof.
 216. A method fortreating nephropathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim158 to a subject in need thereof.
 217. A method for treating neuropathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 159 to a subjectin need thereof.
 218. A method for treating neuropathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 157 to a subject in need thereof.219. A method for treating neuropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 158 to a subject in need thereof.
 220. A compoundhaving the formula:

or a pharmaceutically acceptable salt thereof, wherein R¹ is —CH₂NH—R²,R² is a —C₃-C₈ monocyclic cycloalkyl which is unsubstituted orsubstituted with one or more of-(hydroxy-substituted) C₁-C₅ alkyl; or a3- to 7-membered monocyclic heterocycle; X is halo or —H; and Y′ is haloor —H, wherein at least one of X and Y′ is halo.
 221. The compound or apharmaceutically acceptable salt of the compound of claim 220, whereinR² is tetrahydropyranyl; or cyclopentyl which is unsubstituted orsubstituted with one or more of -(hydroxy-substituted) C₁-C₅ alkyl. 222.The compound or a pharmaceutically acceptable salt of the compound ofclaim 220, wherein one of X and Y′ is fluoro.
 223. A compositioncomprising a physiologically acceptable carrier or vehicle and aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim
 220. 224. A method for treating cancer, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 220 to a subject in need thereof.225. The method of claim 224, further comprising administering aneffective amount of another anticancer agent.
 226. A method for treatingrenal failure, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim220 to a subject in need thereof.
 227. A method for treating areperfusion injury, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim220 to a subject in need thereof.
 228. A method for treating aninflammatory disease, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim220 to a subject in need thereof.
 229. A method for treating diabetesmellitus, comprising administering an effective amount of a compound ora pharmaceutically acceptable salt of a compound of claim 220 to asubject in need thereof.
 230. A method for treating an ischemiccondition, comprising administering an effective amount of a compound ora pharmaceutically acceptable salt of a compound of claim 220 to asubject in need thereof.
 231. A method for treating reoxygenationinjury, comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 232. A method for treating a neurodegenerative disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 233. A method for treating a vascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 234. A method for treating a diabetic complication,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 235. A method for treating a cardiovascular disease,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 236. A method for treating erectile dysfunction,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 237. A method for treating urinary incontinence,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 238. A method for treating a complication ofprematurity, comprising administering an effective amount of a compoundor a pharmaceutically acceptable salt of a compound of claim 220 to asubject in need thereof.
 239. A method for treating cardiomyopathy,comprising administering an effective amount of a compound or apharmaceutically acceptable salt of a compound of claim 220 to a subjectin need thereof.
 240. A method for treating retinopathy, comprisingadministering an effective amount of a compound or a pharmaceuticallyacceptable salt of a compound of claim 220 to a subject in need thereof.241. A method for treating nephropathy, comprising administering aneffective amount of a compound or a pharmaceutically acceptable salt ofa compound of claim 220 to a subject in need thereof.
 242. A method fortreating neuropathy, comprising administering an effective amount of acompound or a pharmaceutically acceptable salt of a compound of claim220 to a subject in need thereof.